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Review Open Access

Metformin prevents the onset and progression of intervertebral disc degeneration: New insights and potential mechanisms (Review)

  • Authors:
    • Wenzhi Yang
    • Yipin Yang
    • Yong Wang
    • Zongshi Gao
    • Jingtang Zhang
    • Weimin Gao
    • Yanjun Chen
    • You Lu
    • Haoyu Wang
    • Lingyan Zhou
    • Yifan Wang
    • Jie Li
    • Hui Tao
  • View Affiliations / Copyright

    Affiliations: Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China, Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China, Department of Clinical Medicine, School of The First Clinical Medicine, Anhui Medical University, Hefei, Anhui 230032, P.R. China, Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China
    Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 71
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    Published online on: July 2, 2024
       https://doi.org/10.3892/ijmm.2024.5395
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Abstract

Metformin has been the go‑to medical treatment for addressing type 2 diabetes mellitus (T2DM) as a frontline oral antidiabetic. Obesity, cancer and bone deterioration are linked to T2DM, which is considered a metabolic illness. Numerous diseases associated with T2DM, such as tumours, cardiovascular disease and bone deterioration, may be treated with metformin. Intervertebral disc degeneration (IVDD) is distinguished by degeneration of the spinal disc, accompanied by the gradual depletion of proteoglycans and water in the nucleus pulposus (NP) of the IVD, resulting in lower back pain. The therapeutic effect of metformin on IVDD has also attracted much attention. By stimulating AMP‑activated kinase, metformin could enhance autophagy and suppress cell senescence, apoptosis and inflammation, thus effectively delaying IVDD. The present review aimed to systematically explain the development of IVDD and mechanism of metformin in the treatment and prevention of IVDD to provide a reference for the clinical application of metformin as adjuvant therapy in the treatment of IVDD.
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1 

Wang F, Cai F, Shi R, Wang XH and Wu XT: Aging and age related stresses: A senescence mechanism of intervertebral disc degeneration. Osteoarthritis Cartilage. 24:398–408. 2016. View Article : Google Scholar

2 

Cornaz F, Widmer J, Farshad-Amacker NA, Spirig JM, Snedeker JG and Farshad M: Biomechanical contributions of spinal structures with different degrees of disc degeneration. Spine (Phila Pa 1976). 46:E869–E877. 2021. View Article : Google Scholar

3 

Lan T, Shiyu H, Shen Z, Yan B and Chen J: New insights into the interplay between miRNAs and autophagy in the aging of intervertebral discs. Ageing Res Rev. 65:1012272021. View Article : Google Scholar

4 

Risbud MV and Shapiro IM: Role of cytokines in intervertebral disc degeneration: Pain and disc content. Nat Rev Rheumatol. 10:44–56. 2014. View Article : Google Scholar

5 

GBD 2019 Diseases and Injuries Collaborators: Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: A systematic analysis for the global burden of disease study 2019. Lancet. 396:1204–1222. 2020. View Article : Google Scholar : PubMed/NCBI

6 

Yang Y, Lai X, Li C, Yang Y, Gu S, Hou W, Zhai L and Zhu Y: Focus on the impact of social factors and lifestyle on the disease burden of low back pain: Findings from the global burden of disease study 2019. BMC Musculoskelet Disord. 24:6792023. View Article : Google Scholar : PubMed/NCBI

7 

Goode AP, Carey TS and Jordan JM: Low back pain and lumbar spine osteoarthritis: How are they related? Curr Rheumatol Rep. 15:3052013. View Article : Google Scholar : PubMed/NCBI

8 

Maher C, Underwood M and Buchbinder R: Non-specific low back pain. Lancet. 389:736–747. 2017. View Article : Google Scholar

9 

Chou R: Low back pain. Ann Intern Med. 174:ITC113–ITC128. 2021. View Article : Google Scholar : PubMed/NCBI

10 

Apostolova N, Iannantuoni F, Gruevska A, Muntane J, Rocha M and Victor VM: Mechanisms of action of metformin in type 2 diabetes: Effects on mitochondria and leukocyte-endothelium interactions. Redox Biol. 34:1015172020. View Article : Google Scholar : PubMed/NCBI

11 

Sanchez-Rangel E and Inzucchi SE: Metformin: Clinical use in type 2 diabetes. Diabetologia. 60:1586–1593. 2017. View Article : Google Scholar : PubMed/NCBI

12 

LaMoia TE and Shulman GI: Cellular and molecular mechanisms of metformin action. Endocr Rev. 42:77–96. 2021. View Article : Google Scholar :

13 

An H and He L: Current understanding of metformin effect on the control of hyperglycemia in diabetes. J Endocrinol. 228:R97–R106. 2016. View Article : Google Scholar : PubMed/NCBI

14 

Foretz M, Hébrard S, Leclerc J, Zarrinpashneh E, Soty M, Mithieux G, Sakamoto K, Andreelli F and Viollet B: Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state. J Clin Invest. 120:2355–2369. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Caton PW, Nayuni NK, Kieswich J, Khan NQ, Yaqoob MM and Corder R: Metformin suppresses hepatic gluconeogenesis through induction of SIRT1 and GCN5. J Endocrinol. 205:97–106. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Kim YD, Park KG, Lee YS, Park YY, Kim DK, Nedumaran B, Jang WG, Cho WJ, Ha J, Lee IK, et al: Metformin inhibits hepatic gluconeogenesis through AMP-activated protein kinase-dependent regulation of the orphan nuclear receptor SHP. Diabetes. 57:306–314. 2008. View Article : Google Scholar

17 

Masarwa R, Brunetti VC, Aloe S, Henderson M, Platt RW and Filion KB: Efficacy and safety of metformin for obesity: A systematic review. Pediatrics. 147:e202016102021. View Article : Google Scholar : PubMed/NCBI

18 

Day EA, Ford RJ, Smith BK, Mohammadi-Shemirani P, Morrow MR, Gutgesell RM, Lu R, Raphenya AR, Kabiri M, McArthur AG, et al: Metformin-induced increases in GDF15 are important for suppressing appetite and promoting weight loss. Nat Metab. 1:1202–1208. 2019. View Article : Google Scholar

19 

Kamarudin MNA, Sarker MMR, Zhou JR and Parhar I: Metformin in colorectal cancer: Molecular mechanism, preclinical and clinical aspects. J Exp Clin Cancer Res. 38:4912019. View Article : Google Scholar : PubMed/NCBI

20 

Luo F, Das A, Chen J, Wu P, Li X and Fang Z: Metformin in patients with and without diabetes: A paradigm shift in cardiovascular disease management. Cardiovasc Diabetol. 18:542019. View Article : Google Scholar : PubMed/NCBI

21 

Griffin SJ, Leaver JK and Irving GJ: Impact of metformin on cardiovascular disease: A meta-analysis of randomised trials among people with type 2 diabetes. Diabetologia. 60:1620–1629. 2017. View Article : Google Scholar : PubMed/NCBI

22 

Diamanti-Kandarakis E, Economou F, Palimeri S and Christakou C: Metformin in polycystic ovary syndrome. Ann N Y Acad Sci. 1205:192–198. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Song A, Zhang C and Meng X: Mechanism and application of metformin in kidney diseases: An update. Biomed Pharmacother. 138:1114542021. View Article : Google Scholar : PubMed/NCBI

24 

Chen S, Gan D, Lin S, Zhong Y, Chen M, Zou X, Shao Z and Xiao G: Metformin in aging and aging-related diseases: Clinical applications and relevant mechanisms. Theranostics. 12:2722–2740. 2022. View Article : Google Scholar : PubMed/NCBI

25 

Lu CH, Chung CH, Kuo FC, Chen KC, Chang CH, Kuo CC, Lee CH, Su SC, Liu JS, Lin FH, et al: Metformin attenuates osteoporosis in diabetic patients with carcinoma in situ: A nationwide, retrospective, matched-cohort study in Taiwan. J Clin Med. 9:28392020. View Article : Google Scholar : PubMed/NCBI

26 

Li J, Zhang B, Liu WX, Lu K, Pan H, Wang T, Oh CD, Yi D, Huang J, Zhao L, et al: Metformin limits osteoarthritis development and progression through activation of AMPK signalling. Ann Rheum Dis. 79:635–645. 2020. View Article : Google Scholar : PubMed/NCBI

27 

Li X, Liu X, Wang Y, Cao F, Chen Z, Hu Z, Yu B, Feng H, Ba Z, Liu T, et al: Intervertebral disc degeneration in mice with type II diabetes induced by leptin receptor deficiency. BMC Musculoskelet Disord. 21:772020. View Article : Google Scholar : PubMed/NCBI

28 

Cannata F, Vadalà G, Ambrosio L, Fallucca S, Napoli N, Papalia R, Pozzilli P and Denaro V: Intervertebral disc degeneration: A focus on obesity and type 2 diabetes. Diabetes Metab Res Rev. 36:e32242020. View Article : Google Scholar

29 

Chen D, Xia D, Pan Z, Xu D, Zhou Y, Wu Y, Cai N, Tang Q, Wang C, Yan M, et al: Metformin protects against apoptosis and senescence in nucleus pulposus cells and ameliorates disc degeneration in vivo. Cell Death Dis. 7:e24412016. View Article : Google Scholar : PubMed/NCBI

30 

Liao Z, Li S, Lu S, Liu H, Li G, Ma L, Luo R, Ke W, Wang B, Xiang Q, et al: Metformin facilitates mesenchymal stem cell-derived extracellular nanovesicles release and optimizes therapeutic efficacy in intervertebral disc degeneration. Biomaterials. 274:1208502021. View Article : Google Scholar : PubMed/NCBI

31 

Ren C, Jin C, Li C, Xiang J, Wu Y, Zhou Y, Sun L, Zhang X and Tian N: Metformin inactivates the cGAS-STING pathway through autophagy and suppresses senescence in nucleus pulposus cells. J Cell Sci. 135:jcs2597382022. View Article : Google Scholar : PubMed/NCBI

32 

Han Y, Yuan F, Deng C, He F, Zhang Y, Shen H, Chen Z and Qian L: Metformin decreases LPS-induced inflammatory response in rabbit annulus fibrosus stem/progenitor cells by blocking HMGB1 release. Aging (Albany NY). 11:1252–10265. 2019.

33 

Ramanathan R, Firdous A, Dong Q, Wang D, Lee J, Vo N and Sowa G: Investigation into the anti-inflammatory properties of metformin in intervertebral disc cells. JOR Spine. 5:e11972022. View Article : Google Scholar : PubMed/NCBI

34 

Kaya YE, Karaarslan N, Yilmaz I, Sirin DY, Akalan H and Ozbek H: A study of the effects of metformin, a biguanide derivative, on annulus fibrosus and nucleus pulposus cells. Turk Neurosurg. 30:434–441. 2020.PubMed/NCBI

35 

Stephenne X, Foretz M, Taleux N, van der Zon GC, Sokal E, Hue L, Viollet B and Guigas B: Metformin activates AMP-activated protein kinase in primary human hepatocytes by decreasing cellular energy status. Diabetologia. 54:3101–3110. 2011. View Article : Google Scholar : PubMed/NCBI

36 

Maruthur NM, Tseng E, Hutfless S, Wilson LM, Suarez-Cuervo C, Berger Z, Yue Chu Y, Iyoha E, Segal JB and Bolen S: Diabetes medications as monotherapy or metformin-based combination therapy for type 2 diabetes: A systematic review and meta-analysis. Ann Intern Med. 164:740–751. 2016. View Article : Google Scholar : PubMed/NCBI

37 

Zhang F, Zhao X, Shen H and Zhang C: Molecular mechanisms of cell death in intervertebral disc degeneration (Review). Int J Mol Med. 37:1439–1448. 2016. View Article : Google Scholar : PubMed/NCBI

38 

Gong CY and Zhang HH: Autophagy as a potential therapeutic target in intervertebral disc degeneration. Life Sci. 273:1192662021. View Article : Google Scholar : PubMed/NCBI

39 

Li J, Wang C, Xue L, Zhang F and Liu J: Melatonin suppresses apoptosis of nucleus pulposus cells through inhibiting autophagy via the PI3K/Akt pathway in a high-glucose culture. Biomed Res Int. 2021:46042582021.PubMed/NCBI

40 

Humzah MD and Soames RW: Human intervertebral disc: Structure and function. Anat Rec. 220:337–356. 1988. View Article : Google Scholar : PubMed/NCBI

41 

Bach FC, de Vries SAH, Krouwels A, Creemers LB, Ito K, Meij BP and Tryfonidou MA: The species-specific regenerative effects of notochordal cell-conditioned medium on chondrocyte-like cells derived from degenerated human intervertebral discs. Eur Cell Mater. 30:132–147. 2015. View Article : Google Scholar : PubMed/NCBI

42 

Urban JPG and Roberts S: Degeneration of the intervertebral disc. Arthritis Res Ther. 5:120–130. 2003. View Article : Google Scholar : PubMed/NCBI

43 

Dowdell J, Erwin M, Choma T, Vaccaro A, Iatridis J and Cho SK: Intervertebral disk degeneration and repair. Neurosurgery. 80(3S): S46–S54. 2017. View Article : Google Scholar : PubMed/NCBI

44 

Oegema TR Jr: Biochemistry of the intervertebral disc. Clin Sports Med. 12:419–439. 1993. View Article : Google Scholar : PubMed/NCBI

45 

Adams MA and Roughley PJ: What is intervertebral disc degeneration, and what causes it? Spine (Phila Pa 1976). 31:2151–2161. 2006. View Article : Google Scholar : PubMed/NCBI

46 

Bruehlmann SB, Rattner JB, Matyas JR and Duncan NA: Regional variations in the cellular matrix of the annulus fibrosus of the intervertebral disc. J Anat. 201:159–171. 2002. View Article : Google Scholar : PubMed/NCBI

47 

Roberts S, Menage J, Duance V, Wotton S and Ayad S: 1991 Volvo Award in basic sciences. Collagen types around the cells of the intervertebral disc and cartilage end plate: An immunolocalization study. Spine (Phila Pa 1976). 16:1030–1038. 1991. View Article : Google Scholar : PubMed/NCBI

48 

Mwale F, Roughley P and Antoniou J: Distinction between the extracellular matrix of the nucleus pulposus and hyaline cartilage: A requisite for tissue engineering of intervertebral disc. Eur Cell Mater. 8:58–64. 2004. View Article : Google Scholar : PubMed/NCBI

49 

Maroudas A, Stockwell RA, Nachemson A and Urban J: Factors involved in the nutrition of the human lumbar intervertebral disc: Cellularity and diffusion of glucose in vitro. J Anat. 120:113–130. 1975.PubMed/NCBI

50 

Yu J, Winlove PC, Roberts S and Urban JPG: Elastic fibre organization in the intervertebral discs of the bovine tail. J Anat. 201:465–475. 2002. View Article : Google Scholar : PubMed/NCBI

51 

Pattappa G, Li Z, Peroglio M, Wismer N, Alini M and Grad S: Diversity of intervertebral disc cells: Phenotype and function. J Anat. 221:480–496. 2012. View Article : Google Scholar : PubMed/NCBI

52 

Moon SM, Yoder JH, Wright AC, Smith LJ, Vresilovic EJ and Elliott DM: Evaluation of intervertebral disc cartilaginous endplate structure using magnetic resonance imaging. Eur Spine J. 22:1820–1828. 2013. View Article : Google Scholar : PubMed/NCBI

53 

Broberg KB: On the mechanical behaviour of intervertebral discs. Spine (Phila Pa 1976). 8:151–165. 1983. View Article : Google Scholar : PubMed/NCBI

54 

Rider SM, Mizuno S and Kang JD: Molecular mechanisms of intervertebral disc degeneration. Spine Surg Relat Res. 3:1–11. 2018. View Article : Google Scholar : PubMed/NCBI

55 

Raj PP: Intervertebral disc: Anatomy-physiology-pathophysiology-treatment. Pain Pract. 8:18–44. 2008. View Article : Google Scholar : PubMed/NCBI

56 

Colombini A, Lombardi G, Corsi MM and Banfi G: Pathophysiology of the human intervertebral disc. Int J Biochem Cell Biol. 40:837–842. 2008. View Article : Google Scholar : PubMed/NCBI

57 

Lyons G, Eisenstein SM and Sweet MB: Biochemical changes in intervertebral disc degeneration. Biochim Biophys Acta. 673:443–453. 1981. View Article : Google Scholar : PubMed/NCBI

58 

Roughley PJ, Melching LI, Heathfield TF, Pearce RH and Mort JS: The structure and degradation of aggrecan in human intervertebral disc. Eur Spine J. 15(Suppl 3): S326–S332. 2006. View Article : Google Scholar : PubMed/NCBI

59 

Binch ALA, Shapiro IM and Risbud MV: Syndecan-4 in intervertebral disc and cartilage: Saint or synner? Matrix Biol. 52-54:355–362. 2016. View Article : Google Scholar : PubMed/NCBI

60 

Xu K, Wang X, Zhang Q, Liang A, Zhu H, Huang D, Li C and Ye W: Sp1 downregulates proinflammatory cytokine-induced catabolic gene expression in nucleus pulposus cells. Mol Med Rep. 14:3961–3968. 2016. View Article : Google Scholar : PubMed/NCBI

61 

Roughley PJ: Biology of intervertebral disc aging and degeneration: Involvement of the extracellular matrix. Spine (Phila Pa 1976). 29:2691–2699. 2004. View Article : Google Scholar : PubMed/NCBI

62 

Sjöberg AP, Manderson GA, Mörgelin M, Day AJ, Heinegård D and Blom AM: Short leucine-rich glycoproteins of the extracellular matrix display diverse patterns of complement interaction and activation. Mol Immunol. 46:830–839. 2009. View Article : Google Scholar :

63 

Huang YC, Urban JP and Luk KD: Intervertebral disc regeneration: Do nutrients lead the way? Nat Rev Rheumatol. 10:561–566. 2014. View Article : Google Scholar : PubMed/NCBI

64 

Zhang H, Zhu T, Zhang L and Wu Q: Stromal cell-derived factor-1 induces matrix metalloproteinase expression in human endplate chondrocytes, cartilage endplate degradation in explant culture, and the amelioration of nucleus pulposus degeneration in vivo. Int J Mol Med. 41:969–976. 2018.

65 

Hiyama A, Sakai D and Mochida J: Cell signaling pathways related to pain receptors in the degenerated disk. Global Spine J. 3:165–174. 2013. View Article : Google Scholar :

66 

Kondo N, Yuasa T, Shimono K, Tung W, Okabe T, Yasuhara R, Pacifici M, Zhang Y, Iwamoto M and Enomoto-Iwamoto M: Intervertebral disc development is regulated by Wnt/β-catenin signaling. Spine (Phila Pa 1976). 36:E513–E518. 2011. View Article : Google Scholar : PubMed/NCBI

67 

Lotz JC and Ulrich JA: Innervation, inflammation, and hypermobility may characterize pathologic disc degeneration: review of animal model data. J Bone Joint Surg Am. 88(Suppl 2): S76–S82. 2006.

68 

Finkel T and Holbrook NJ: Oxidants, oxidative stress and the biology of ageing. Nature. 408:239–247. 2000. View Article : Google Scholar : PubMed/NCBI

69 

Olovnikov AM: A theory of marginotomy. The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon. J Theor Biol. 41:181–190. 1973. View Article : Google Scholar : PubMed/NCBI

70 

Stein GH, Beeson M and Gordon L: Failure to phosphorylate the retinoblastoma gene product in senescent human fibroblasts. Science. 249:666–669. 1990. View Article : Google Scholar : PubMed/NCBI

71 

Feng C, Yang M, Lan M, Liu C, Zhang Y, Huang B, Liu H and Zhou Y: ROS: Crucial intermediators in the pathogenesis of intervertebral disc degeneration. Oxid Med Cell Longev. 2017:56015932017. View Article : Google Scholar : PubMed/NCBI

72 

Dimozi A, Mavrogonatou E, Sklirou A and Kletsas D: Oxidative stress inhibits the proliferation, induces premature senescence and promotes a catabolic phenotype in human nucleus pulposus intervertebral disc cells. Eur Cell Mater. 30:89–103. 2015. View Article : Google Scholar : PubMed/NCBI

73 

Feng C, Liu H, Yang M, Zhang Y, Huang B and Zhou Y: Disc cell senescence in intervertebral disc degeneration: Causes and molecular pathways. Cell Cycle. 15:1674–1684. 2016. View Article : Google Scholar : PubMed/NCBI

74 

Wang D, Hu Z, Hao J, He B, Gan Q, Zhong X, Zhang X, Shen J, Fang J and Jiang W: SIRT1 inhibits apoptosis of degenerative human disc nucleus pulposus cells through activation of Akt pathway. Age (Dordr). 35:1741–1753. 2013. View Article : Google Scholar

75 

Chen JW, Ni BB, Zheng XF, Li B, Jiang SD and Jiang LS: Hypoxia facilitates the survival of nucleus pulposus cells in serum deprivation by down-regulating excessive autophagy through restricting ROS generation. Int J Biochem Cell Biol. 59:1–10. 2015. View Article : Google Scholar

76 

Kim J, Kundu M, Viollet B and Guan KL: AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol. 13:132–141. 2011. View Article : Google Scholar : PubMed/NCBI

77 

Xu HG, Yu YF, Zheng Q, Zhang W, Wang CD, Zhao XY, Tong WX, Wang H, Liu P and Zhang XL: Autophagy protects end plate chondrocytes from intermittent cyclic mechanical tension induced calcification. Bone. 66:232–239. 2014. View Article : Google Scholar : PubMed/NCBI

78 

Wada T and Penninger JM: Mitogen-activated protein kinases in apoptosis regulation. Oncogene. 23:2838–2849. 2004. View Article : Google Scholar : PubMed/NCBI

79 

Deosarkar SD, Arsule AD and Kalyankar TM: Effect of antidiabetic metformin hydrochloride on physicochemical properties of cationic surfactant cetyltrimethylammonium bromide in aqueous solutions. Colloids Surf A: Physicochem Eng Asp. 613:1260522021. View Article : Google Scholar

80 

Dołowy M, Jampilek J and Bober-Majnusz K: A comparative study of the lipophilicity of metformin and phenformin. Molecules. 26:66132021. View Article : Google Scholar :

81 

Ismail AH, Al-Garawi ZS, Al-Shamari K and Salman AT: Metformin compounds: A review on the importance and the possible applications. J Phys Conf Ser. 1853:0120602021. View Article : Google Scholar

82 

He M, Lu B, Opoku M, Zhang L, Xie W, Jin H, Chen S, Li Y and Deng Z: Metformin prevents or delays the development and progression of osteoarthritis: New insight and mechanism of action. Cells. 11:30122022. View Article : Google Scholar : PubMed/NCBI

83 

Graham GG, Punt J, Arora M, Day RO, Doogue MP, Duong JK, Furlong TJ, Greenfield JR, Greenup LC, Kirkpatrick CM, et al: Clinical pharmacokinetics of metformin. Clin Pharmacokinet. 50:81–98. 2011. View Article : Google Scholar : PubMed/NCBI

84 

Bailey CJ: Metformin: Historical overview. Diabetologia. 60:1566–1576. 2017. View Article : Google Scholar : PubMed/NCBI

85 

He L: Metformin and systemic metabolism. Trends Pharmacol Sci. 41:868–881. 2020. View Article : Google Scholar : PubMed/NCBI

86 

Tucker GT, Casey C, Phillips PJ, Connor H, Ward JD and Woods HF: Metformin kinetics in healthy subjects and in patients with diabetes mellitus. Br J Clin Pharmacol. 12:235–246. 1981. View Article : Google Scholar : PubMed/NCBI

87 

Wilcock C and Bailey CJ: Accumulation of metformin by tissues of the normal and diabetic mouse. Xenobiotica. 24:49–57. 1994. View Article : Google Scholar : PubMed/NCBI

88 

Sambol NC, Brookes LG, Chiang J, Goodman AM, Lin ET, Liu CY and Benet LZ: Food intake and dosage level, but not tablet vs solution dosage form, affect the absorption of metformin HCl in man. Br J Clin Pharmacol. 42:510–512. 1996. View Article : Google Scholar : PubMed/NCBI

89 

Song Y, Wu Z and Zhao P: The function of metformin in aging-related musculoskeletal disorders. Front Pharmacol. 13:8655242022. View Article : Google Scholar : PubMed/NCBI

90 

Chen S, Ruan G, Zeng M, Chen T, Cao P, Zhang Y, Li J, Wang X, Li S, Tang S, et al: Association between metformin use and risk of total knee arthroplasty and degree of knee pain in knee osteoarthritis patients with diabetes and/or obesity: A retrospective study. J Clin Med. 11:47962022. View Article : Google Scholar : PubMed/NCBI

91 

El-Arabey AA, Abdalla M and Ali Eltayb W: Metformin: Ongoing journey with superdrug revolution. Adv Pharm Bull. 9:1–4. 2019. View Article : Google Scholar : PubMed/NCBI

92 

Mazor M, Best TM, Cesaro A, Lespessailles E and Toumi H: Osteoarthritis biomarker responses and cartilage adaptation to exercise: A review of animal and human models. Scand J Med Sci Sports. 29:1072–1082. 2019. View Article : Google Scholar : PubMed/NCBI

93 

Vinatier C, Merceron C and Guicheux J: Osteoarthritis: From pathogenic mechanisms and recent clinical developments to novel prospective therapeutic options. Drug Discov Today. 21:1932–1937. 2016. View Article : Google Scholar : PubMed/NCBI

94 

Williams S, Alkhatib B and Serra R: Development of the axial skeleton and intervertebral disc. Curr Top Dev Biol. 133:49–90. 2019. View Article : Google Scholar : PubMed/NCBI

95 

Li X, Lee JP, Balian G and Greg Anderson D: Modulation of chondrocytic properties of fat-derived mesenchymal cells in co-cultures with nucleus pulposus. Connect Tissue Res. 46:75–82. 2005. View Article : Google Scholar : PubMed/NCBI

96 

Jørgensen SB, Richter EA and Wojtaszewski JF: Role of AMPK in skeletal muscle metabolic regulation and adaptation in relation to exercise. J Physiol. 574:17–31. 2006. View Article : Google Scholar : PubMed/NCBI

97 

Lee WJ, Kim M, Park HS, Kim HS, Jeon MJ, Oh KS, Koh EH, Won JC, Kim MS, Oh GT, et al: AMPK activation increases fatty acid oxidation in skeletal muscle by activating PPARalpha and PGC-1. Biochem Biophys Res Commun. 340:291–295. 2006. View Article : Google Scholar

98 

Lee-Young RS, Canny BJ, Myers DE and McConell GK: AMPK activation is fiber type specific in human skeletal muscle: effects of exercise and short-term exercise training. J Appl Physiol (1985). 107:283–289. 2009. View Article : Google Scholar : PubMed/NCBI

99 

Bahrambeigi S, Yousefi B, Rahimi M and Shafiei-Irannejad V: Metformin; an old antidiabetic drug with new potentials in bone disorders. Biomed Pharmacother. 109:1593–1601. 2019. View Article : Google Scholar

100 

Qin X, Jiang T, Liu S, Tan J, Wu H, Zheng L and Zhao J: Effect of metformin on ossification and inflammation of fibroblasts in ankylosing spondylitis: An in vitro study. J Cell Biochem. 119:1074–1082. 2018. View Article : Google Scholar

101 

Ma T, Tian X, Zhang B, Li M, Wang Y, Yang C, Wu J, Wei X, Qu Q, Yu Y, et al: Low-dose metformin targets the lysosomal AMPK pathway through PEN2. Nature. 603:159–165. 2022. View Article : Google Scholar : PubMed/NCBI

102 

Sakamoto K and Jessen N: PEN2: Metformin's new partner at lysosome. Cell Res. 32:507–508. 2022. View Article : Google Scholar : PubMed/NCBI

103 

Liu C, Zhang S, Xue J, Zhang H and Yin J: Evaluation of PEN2-ATP6AP1 axis as an antiparasitic target for metformin based on phylogeny analysis and molecular docking. Mol Biochem Parasitol. 255:1115802023. View Article : Google Scholar : PubMed/NCBI

104 

Dong J, Xu X, Zhang Q, Yuan Z and Tan B: The PI3K/AKT pathway promotes fracture healing through its crosstalk with Wnt/β-catenin. Exp Cell Res. 394:1121372020. View Article : Google Scholar

105 

Watabe H, Furuhama T, Tani-Ishii N and Mikuni-Takagaki Y: Mechanotransduction activates α5β1 integrin and PI3K/Akt signaling pathways in mandibular osteoblasts. Exp Cell Res. 317:2642–2649. 2011. View Article : Google Scholar : PubMed/NCBI

106 

Wang Z, Ma F, Wang J, Zhou Z, Liu B, He X, Fu L, He W and Cooper PR: Extracellular signal-regulated kinase mitogen-activated protein kinase and phosphatidylinositol 3-kinase/Akt signaling are required for lipopolysaccharide-mediated mineralization in murine odontoblast-like cells. J Endod. 41:871–876. 2015. View Article : Google Scholar : PubMed/NCBI

107 

Tang Y, Mo Y, Xin D, Xiong Z, Zeng L, Luo G and Cao Y: Regulation of osteoblast autophagy based on PI3K/AKT/mTOR signaling pathway study on the effect of β-ecdysterone on fracture healing. J Orthop Surg Res. 16:7192021. View Article : Google Scholar

108 

Lee SH, Lee JH, Lee HY and Min KJ: Sirtuin signaling in cellular senescence and aging. BMB Rep. 52:24–34. 2019. View Article : Google Scholar :

109 

Hu X, Feng G, Meng Z, Ma L and Jin Q: The protective mechanism of SIRT1 on cartilage through regulation of LEF-1. BMC Musculoskelet Disord. 22:6422021. View Article : Google Scholar : PubMed/NCBI

110 

Wang C, Yang Y, Zhang Y, Liu J, Yao Z and Zhang C: Protective effects of metformin against osteoarthritis through upregulation of SIRT3-mediated PINK1/Parkin-dependent mitophagy in primary chondrocytes. Biosci Trends. 12:605–612. 2019. View Article : Google Scholar

111 

Chen Y, Wu YY, Si HB, Lu YR and Shen B: Mechanistic insights into AMPK-SIRT3 positive feedback loop-mediated chondrocyte mitochondrial quality control in osteoarthritis pathogenesis. Pharmacol Res. 166:1054972021. View Article : Google Scholar : PubMed/NCBI

112 

Lin S, Guo H, You X, Zhang Z and Ye H: SND1 aggravates mitochondrial damage, apoptosis and extracellular matrix degradation in IL-1β-stimulated chondrocytes via PINK1/BECN1 pathway. Eur J Med Res. 28:3712023. View Article : Google Scholar

113 

Hu D, Xie F, Xiao Y, Lu C, Zhong J, Huang D, Chen J, Wei J, Jiang Y and Zhong T: Metformin: A potential candidate for targeting aging mechanisms. Aging Dis. 12:480–493. 2021. View Article : Google Scholar : PubMed/NCBI

114 

Xing H, Liang C, Wang C, Xu X, Hu Y and Qiu B: Metformin mitigates cholesterol accumulation via the AMPK/SIRT1 pathway to protect osteoarthritis chondrocytes. Biochem Biophys Res Commun. 632:113–121. 2022. View Article : Google Scholar : PubMed/NCBI

115 

Kang W, Wang T, Hu Z, Liu F, Sun Y and Ge S: Metformin inhibits porphyromonas gingivalis lipopolysaccharide-influenced inflammatory response in human gingival fibroblasts via regulating activating transcription factor-3 expression. J Periodontol. 88:e169–e178. 2017. View Article : Google Scholar : PubMed/NCBI

116 

Saluja M, Pareek KK and Swami YK: Study of diversity of metformin related gastrointestinal side effects. J Assoc Physicians India. 68:36–38. 2020.PubMed/NCBI

117 

Lamos EM, Stein SA and Davis SN: Combination of glibenclamide-metformin HCl for the treatment of type 2 diabetes mellitus. Expert Opin Pharmacother. 13:2545–2554. 2012. View Article : Google Scholar : PubMed/NCBI

118 

Stades AME, Heikens JT, Erkelens DW, Holleman F and Hoekstra JBL: Metformin and lactic acidosis: Cause or coincidence? A review of case reports. J Intern Med. 255:179–187. 2004. View Article : Google Scholar : PubMed/NCBI

119 

Eppenga WL, Lalmohamed A, Geerts AF, Derijks HJ, Wensing M, Egberts A, De Smet PA and de Vries F: Risk of lactic acidosis or elevated lactate concentrations in metformin users with renal impairment: A population-based cohort study. Diabetes Care. 37:2218–2224. 2014. View Article : Google Scholar : PubMed/NCBI

120 

O CK, Siu BW, Leung VW, Lin YY, Ding CZ, Lau ES, Luk AO, Chow EY, Ma RC, Chan JC, et al: Association of insomnia with incident chronic cognitive impairment in older adults with type 2 diabetes mellitus: A prospective study of the Hong Kong diabetes register. J Diabetes Complications. 37:1085982023. View Article : Google Scholar : PubMed/NCBI

121 

Wiwanitkit S and Wiwanitkit V: Metformin and sleep disorders. Indian J Endocrinol Metab. 16(Suppl 1): S63–S64. 2012. View Article : Google Scholar : PubMed/NCBI

122 

Rosekind MR and Gregory KB: Insomnia risks and costs: health, safety, and quality of life. Am J Manag Care. 16:617–626. 2010.PubMed/NCBI

123 

Wu H, Esteve E, Tremaroli V, Khan MT, Caesar R, Mannerås-Holm L, Ståhlman M, Olsson LM, Serino M, Planas-Fèlix M, et al: Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nat Med. 23:850–858. 2017. View Article : Google Scholar : PubMed/NCBI

124 

Salvatore T, Pafundi PC, Marfella R, Sardu C, Rinaldi L, Monaco L, Ricozzi C, Imbriani S, Nevola R, Adinolfi LE and Sasso FC: Metformin lactic acidosis: Should we still be afraid? Diabetes Res Clin Pract. 157:1078792019. View Article : Google Scholar : PubMed/NCBI

125 

Rahman F and Tuba S: Lactic acidosis associated with metformin in patients with diabetic kidney disease. Med Arch. 76:297–300. 2022. View Article : Google Scholar : PubMed/NCBI

126 

Hardie DG, Ross FA and Hawley SA: AMPK: A nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol. 13:251–262. 2012. View Article : Google Scholar : PubMed/NCBI

127 

Du J, Xu M, Kong F, Zhu P, Mao Y, Liu Y, Zhou H, Dong Z, Yu Z, Du T, et al: CB2R attenuates intervertebral disc degeneration by delaying nucleus pulposus cell senescence through AMPK/GSK3β pathway. Aging Dis. 13:552–267. 2022. View Article : Google Scholar : PubMed/NCBI

128 

Zhang Z, Wu J, Teng C, Wang J, Yu J, Jin C, Wang L, Wu L and Lin Z, Yu Z and Lin Z: Orientin downregulating oxidative stress-mediated endoplasmic reticulum stress and mitochondrial dysfunction through AMPK/SIRT1 pathway in rat nucleus pulposus cells in vitro and attenuated intervertebral disc degeneration in vivo. Apoptosis. 27:1031–1048. 2022. View Article : Google Scholar : PubMed/NCBI

129 

Harada M, Tadevosyan A, Qi X, Xiao J, Liu T, Voigt N, Karck M, Kamler M, Kodama I, Murohara T, et al: Atrial fibrillation activates AMP-dependent protein kinase and its regulation of cellular calcium handling: Potential role in metabolic adaptation and prevention of progression. J Am Coll Cardiol. 66:47–58. 2015. View Article : Google Scholar : PubMed/NCBI

130 

Zhang GZ, Deng YJ, Xie QQ, Ren EH, Ma ZJ, He XG, Gao YC and Kang XW: Sirtuins and intervertebral disc degeneration: Roles in inflammation, oxidative stress, and mitochondrial function. Clin Chim Acta. 508:33–42. 2020. View Article : Google Scholar : PubMed/NCBI

131 

Liu Y, Lin J, Wu X, Guo X, Sun H, Yu B, Shen J, Bai J, Chen Z, Yang H, et al: Aspirin-mediated attenuation of intervertebral disc degeneration by ameliorating reactive oxygen species in vivo and in vitro. Oxid Med Cell Longev. 2019:71898542019. View Article : Google Scholar : PubMed/NCBI

132 

Dai X, Chen Y, Yu Z, Liao C, Liu Z, Chen J and Wu Q: Advanced oxidation protein products induce annulus fibrosus cell senescence through a NOX4-dependent, MAPK-mediated pathway and accelerate intervertebral disc degeneration. PeerJ. 10:e138262022. View Article : Google Scholar : PubMed/NCBI

133 

Chen JW, Ni BB, Li B, Yang YH, Jiang SD and Jiang LS: The responses of autophagy and apoptosis to oxidative stress in nucleus pulposus cells: Implications for disc degeneration. Cell Physiol Biochem. 34:1175–1189. 2014. View Article : Google Scholar : PubMed/NCBI

134 

Brennan MÁ, Layrolle P and Mooney DJ: Biomaterials functionalized with MSC secreted extracellular vesicles and soluble factors for tissue regeneration. Adv Funct Mater. 30:19091252020. View Article : Google Scholar : PubMed/NCBI

135 

Varderidou-Minasian S and Lorenowicz MJ: Mesenchymal stromal/stem cell-derived extracellular vesicles in tissue repair: Challenges and opportunities. Theranostics. 10:5979–5997. 2020. View Article : Google Scholar : PubMed/NCBI

136 

Rani S, Ryan AE, Griffin MD and Ritter T: Mesenchymal stem cell-derived extracellular vesicles: Toward cell-free therapeutic applications. Mol Ther. 23:812–823. 2015. View Article : Google Scholar : PubMed/NCBI

137 

Latifkar A, Ling L, Hingorani A, Johansen E, Clement A, Zhang X, Hartman J, Fischbach C, Lin H, Cerione RA and Antonyak MA: Loss of sirtuin 1 alters the secretome of breast cancer cells by impairing lysosomal integrity. Dev Cell. 49:393–408.e7. 2019. View Article : Google Scholar : PubMed/NCBI

138 

Minakaki G, Menges S, Kittel A, Emmanouilidou E, Schaeffner I, Barkovits K, Bergmann A, Rockenstein E, Adame A, Marxreiter F, et al: Autophagy inhibition promotes SNCA/alpha-synuclein release and transfer via extracellular vesicles with a hybrid autophagosome-exosome-like phenotype. Autophagy. 14:98–119. 2018. View Article : Google Scholar :

139 

Wang Y, Xu W, Yan Z, Zhao W, Mi J, Li J and Yan H: Metformin induces autophagy and G0/G1 phase cell cycle arrest in myeloma by targeting the AMPK/mTORC1 and mTORC2 pathways. J Exp Clin Cancer Res. 37:632018. View Article : Google Scholar : PubMed/NCBI

140 

Shen M, Yu H, Jin Y, Mo J, Sui J, Qian X and Chen T: Metformin facilitates osteoblastic differentiation and M2 macrophage polarization by PI3K/AKT/mTOR pathway in human umbilical cord mesenchymal stem cells. Stem Cells Int. 2022:94988762022. View Article : Google Scholar : PubMed/NCBI

141 

Han X, Chen H, Gong H, Tang X, Huang N, Xu W, Tai H, Zhang G, Zhao T, Gong C, et al: Autolysosomal degradation of cytosolic chromatin fragments antagonizes oxidative stress-induced senescence. J Biol Chem. 295:4451–4463. 2020. View Article : Google Scholar : PubMed/NCBI

142 

Tang Z, Hu B, Zang F, Wang J, Zhang X and Chen H: Nrf2 drives oxidative stress-induced autophagy in nucleus pulposus cells via a Keap1/Nrf2/p62 feedback loop to protect intervertebral disc from degeneration. Cell Death Dis. 10:5102019. View Article : Google Scholar : PubMed/NCBI

143 

Wang J, Huang C, Lin Z, Pan X, Chen J, Zheng G, Tian N, Yan Y, Zhang Z, Hu J, et al: Polydatin suppresses nucleus pulposus cell senescence, promotes matrix homeostasis and attenuates intervertebral disc degeneration in rats. J Cell Mol Med. 22:5720–5731. 2018. View Article : Google Scholar : PubMed/NCBI

144 

Kang L, Zhang H, Jia C, Zhang R and Shen C: Targeting oxidative stress and inflammation in intervertebral disc degeneration: Therapeutic perspectives of phytochemicals. Front Pharmacol. 13:9563552022. View Article : Google Scholar : PubMed/NCBI

145 

Glück S, Guey B, Gulen MF, Wolter K, Kang TW, Schmacke NA, Bridgeman A, Rehwinkel J, Zender L and Ablasser A: Innate immune sensing of cytosolic chromatin fragments through cGAS promotes senescence. Nat Cell Biol. 19:1061–1070. 2017. View Article : Google Scholar : PubMed/NCBI

146 

Cheng Z, Dai T, He X, Zhang Z, Xie F, Wang S, Zhang L and Zhou F: The interactions between cGAS-STING pathway and pathogens. Signal Transduct Target Ther. 5:912020. View Article : Google Scholar : PubMed/NCBI

147 

Chen Q, Sun L and Chen ZJ: Regulation and function of the cGAS-STING pathway of cytosolic DNA sensing. Nat Immunol. 17:1142–1149. 2016. View Article : Google Scholar : PubMed/NCBI

148 

Hu MM and Shu HB: Innate immune response to cytoplasmic DNA: Mechanisms and DIseases. Annu Rev Immunol. 38:79–98. 2020. View Article : Google Scholar

149 

Motwani M, Pesiridis S and Fitzgerald KA: DNA sensing by the cGAS-STING pathway in health and disease. Nat Rev Genet. 20:657–674. 2019. View Article : Google Scholar : PubMed/NCBI

150 

Kim J, Kim HS and Chung JH: Molecular mechanisms of mitochondrial DNA release and activation of the cGAS-STING pathway. Exp Mol Med. 55:510–519. 2023. View Article : Google Scholar : PubMed/NCBI

151 

Guo Y, Gu R, Gan D, Hu F, Li G and Xu G: Mitochondrial DNA drives noncanonical inflammation activation via cGAS-STING signaling pathway in retinal microvascular endothelial cells. Cell Commun Signal. 18:1722020. View Article : Google Scholar : PubMed/NCBI

152 

Ritchie C, Carozza JA and Li L: Biochemistry, cell biology, and pathophysiology of the innate immune cGAS-cGAMP-STING pathway. Annu Rev Biochem. 91:599–628. 2022. View Article : Google Scholar : PubMed/NCBI

153 

Lawrence T: The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol. 1:a0016512009. View Article : Google Scholar

154 

Vo NV, Sowa GA, Kang JD, Seidel C and Studer RK: Prostaglandin E2 and prostaglandin F2α differentially modulate matrix metabolism of human nucleus pulposus cells. J Orthop Res. 28:1259–1266. 2010. View Article : Google Scholar : PubMed/NCBI

155 

Tisherman R, Coelho P, Phillibert D, Wang D, Dong Q, Vo N, Kang J and Sowa G: NF-κB signaling pathway in controlling intervertebral disk cell response to inflammatory and mechanical stressors. Phys Ther. 96:704–711. 2016. View Article : Google Scholar : PubMed/NCBI

156 

Ren H, Shao Y, Wu C, Ma X, Lv C and Wang Q: Metformin alleviates oxidative stress and enhances autophagy in diabetic kidney disease via AMPK/SIRT1-FoxO1 pathway. Mol Cell Endocrinol. 500:1106282020. View Article : Google Scholar

157 

Chen Q, Guan X, Zuo X, Wang J and Yin W: The role of high mobility group box 1 (HMGB1) in the pathogenesis of kidney diseases. Acta Pharm Sin B. 6:183–188. 2016. View Article : Google Scholar : PubMed/NCBI

158 

Tang D, Kang R, Van Houten B, Zeh HJ, Billiar TR and Lotze MT: High mobility group box 1 (HMGB1) phenotypic role revealed with stress. Mol Med. 20:359–362. 2014. View Article : Google Scholar : PubMed/NCBI

159 

Leclerc P, Wähämaa H, Idborg H, Jakobsson PJ, Harris HE and Korotkova M: IL-1β/HMGB1 complexes promote The PGE2 biosynthesis pathway in synovial fibroblasts. Scand J Immunol. 77:350–360. 2013. View Article : Google Scholar : PubMed/NCBI

160 

Appavoo E, Hajam IA, Muneeswaran NS, Kondabattula G, Bhanuprakash V and Kishore S: Synergistic effect of high-mobility group box-1 and lipopolysaccharide on cytokine induction in bovine peripheral blood mononuclear cells. Microbiol Immunol. 60:196–202. 2016. View Article : Google Scholar

161 

Wang Y, Che M, Xin J, Zheng Z, Li J and Zhang S: The role of IL-1β and TNF-α in intervertebral disc degeneration. Biomed Pharmacother. 131:1106602020. View Article : Google Scholar

162 

Song Y, Wang Y, Zhang Y, Geng W, Liu W, Gao Y, Li S, Wang K, Wu X, Kang L and Yang C: Advanced glycation end products regulate anabolic and catabolic activities via NLRP3-inflammasome activation in human nucleus pulposus cells. J Cell Mol Med. 21:1373–1387. 2017. View Article : Google Scholar : PubMed/NCBI

163 

Dong HC, Li PN, Chen CJ, Xu X, Zhang H, Liu G, Zheng LJ and Li P: Sinomenine attenuates cartilage degeneration by regulating miR-223-3p/NLRP3 inflammasome signaling. Inflammation. 42:1265–1275. 2019. View Article : Google Scholar : PubMed/NCBI

164 

Xu H, Mei Q, Xu B, Liu G and Zhao J: Expression of matrix metalloproteinases is positively related to the severity of disc degeneration and growing age in the East Asian lumbar disc herniation patients. Cell Biochem Biophys. 70:1219–1225. 2014. View Article : Google Scholar : PubMed/NCBI

165 

Vo NV, Hartman RA, Yurube T, Jacobs LJ, Sowa GA and Kang JD: Expression and regulation of metalloproteinases and their inhibitors in intervertebral disc aging and degeneration. Spine J. 13:331–341. 2013. View Article : Google Scholar : PubMed/NCBI

166 

Liu Q, Jin L, Shen FH, Balian G and Li XJ: Fullerol nanoparticles suppress inflammatory response and adipogenesis of vertebral bone marrow stromal cells-a potential novel treatment for intervertebral disc degeneration. Spine J. 13:1571–1580. 2013. View Article : Google Scholar : PubMed/NCBI

167 

Xian H, Liu Y, Rundberg Nilsson A, Gatchalian R, Crother TR, Tourtellotte WG, Zhang Y, Aleman-Muench GR, Lewis G, Chen W, et al: Metformin inhibition of mitochondrial ATP and DNA synthesis abrogates NLRP3 inflammasome activation and pulmonary inflammation. Immunity. 54:1463–1477.e11. 2021. View Article : Google Scholar : PubMed/NCBI

168 

Jiang Y, Xie Z, Yu J and Fu L: Resveratrol inhibits IL-1β-mediated nucleus pulposus cell apoptosis through regulating the PI3K/Akt pathway. Biosci Rep. 39:BSR201900432019. View Article : Google Scholar

169 

Isoda K, Young JL, Zirlik A, MacFarlane LA, Tsuboi N, Gerdes N, Schönbeck U and Libby P: Metformin inhibits proinflammatory responses and nuclear factor-kappaB in human vascular wall cells. Arterioscler Thromb Vasc Biol. 26:611–617. 2006. View Article : Google Scholar

170 

Carafa V, Rotili D, Forgione M, Cuomo F, Serretiello E, Hailu GS, Jarho E, Lahtela-Kakkonen M, Mai A and Altucci L: Sirtuin functions and modulation: From chemistry to the clinic. Clin Epigenetics. 8:612016. View Article : Google Scholar : PubMed/NCBI

171 

Dai H, Sinclair DA, Ellis JL and Steegborn C: Sirtuin activators and inhibitors: Promises, achievements, and challenges. Pharmacol Ther. 188:140–154. 2018. View Article : Google Scholar : PubMed/NCBI

172 

Ohguchi K, Itoh T, Akao Y, Inoue H, Nozawa Y and Ito M: SIRT1 modulates expression of matrix metalloproteinases in human dermal fibroblasts. Br J Dermatol. 163:689–694. 2010. View Article : Google Scholar : PubMed/NCBI

173 

Dvir-Ginzberg M, Gagarina V, Lee EJ and Hall DJ: Regulation of cartilage-specific gene expression in human chondrocytes by SirT1 and nicotinamide phosphoribosyltransferase. J Biol Chem. 283:36300–36310. 2008. View Article : Google Scholar : PubMed/NCBI

174 

Qu L, Yu Y, Qiu L, Yang D, Yan L, Guo J and Jahan R: Sirtuin 1 regulates matrix metalloproteinase-13 expression induced by Porphyromonas endodontalis lipopolysaccharide via targeting nuclear factor-κB in osteoblasts. J Oral Microbiol. 9:13175782017. View Article : Google Scholar

175 

Abdelmawgoud H and El Awady RR: Effect of Sirtuin 1 inhibition on matrix metalloproteinase 2 and Forkhead box O3a expression in breast cancer cells. Genes Dis. 4:240–246. 2017. View Article : Google Scholar

176 

Gagarina V, Gabay O, Dvir-Ginzberg M, Lee EJ, Brady JK, Quon MJ and Hall DJ: SirT1 enhances survival of human osteoarthritic chondrocytes by repressing protein tyrosine phosphatase 1B and activating the insulin-like growth factor receptor pathway. Arthritis Rheum. 62:1383–1392. 2010. View Article : Google Scholar : PubMed/NCBI

177 

Song YM, Lee YH, Kim JW, Ham DS, Kang ES, Cha BS, Lee HC and Lee BW: Metformin alleviates hepatosteatosis by restoring SIRT1-mediated autophagy induction via an AMP-activated protein kinase-independent pathway. Autophagy. 11:46–59. 2015. View Article : Google Scholar :

178 

Rogacka D, Audzeyenka I, Rychłowski M, Rachubik P, Szrejder M, Angielski S and Piwkowska A: Metformin overcomes high glucose-induced insulin resistance of podocytes by pleiotropic effects on SIRT1 and AMPK. Biochim Biophys Acta Mol Basis Dis. 1864:115–125. 2018. View Article : Google Scholar

179 

Shen J, Lan Y, Ji Z and Liu H: Sirtuins in intervertebral disc degeneration: Current understanding. Mol Med. 30:442024. View Article : Google Scholar : PubMed/NCBI

180 

Xu J, Shao T, Lou J, Zhang J and Xia C: Aging, cell senescence, the pathogenesis and targeted therapies of intervertebral disc degeneration. Front Pharmacol. 14:11729202023. View Article : Google Scholar : PubMed/NCBI

181 

Song Y, Li S, Geng W, Luo R, Liu W, Tu J, Wang K, Kang L, Yin H, Wu X, et al: Sirtuin 3-dependent mitochondrial redox homeostasis protects against AGEs-induced intervertebral disc degeneration. Redox Biol. 19:339–353. 2018. View Article : Google Scholar : PubMed/NCBI

182 

Lin J, Du J, Wu X, Xu C, Liu J, Jiang L, Cheng X, Ge G, Chen L, Pang Q, et al: SIRT3 mitigates intervertebral disc degeneration by delaying oxidative stress-induced senescence of nucleus pulposus cells. J Cell Physiol. 236:6441–6456. 2021. View Article : Google Scholar : PubMed/NCBI

183 

Hu B, Wang P, Zhang S, Liu W, Lv X, Shi D, Zhao L, Liu H, Wang B, Chen S and Shao Z: HSP70 attenuates compression-induced apoptosis of nucleus pulposus cells by suppressing mitochondrial fission via upregulating the expression of SIRT3. Exp Mol Med. 54:309–323. 2022. View Article : Google Scholar : PubMed/NCBI

184 

Zhou TY, Wu YG, Zhang YZ, Bao YW and Zhao Y: SIRT3 retards intervertebral disc degeneration by anti-oxidative stress by activating the SIRT3/FOXO3/SOD2 signaling pathway. Eur Rev Med Pharmacol Sci. 23:9180–9188. 2019.PubMed/NCBI

185 

Karnewar S, Neeli PK, Panuganti D, Kotagiri S, Mallappa S, Jain N, Jerald MK and Kotamraju S: Metformin regulates mitochondrial biogenesis and senescence through AMPK mediated H3K79 methylation: Relevance in age-associated vascular dysfunction. Biochim Biophys Acta Mol Basis Dis. 1864:1115–1128. 2018. View Article : Google Scholar : PubMed/NCBI

186 

Du Y and Zhang J, Fang F, Wei X, Zhang H, Tan H and Zhang J: Metformin ameliorates hypoxia/reoxygenation-induced cardio-myocyte apoptosis based on the SIRT3 signaling pathway. Gene. 626:182–188. 2017. View Article : Google Scholar : PubMed/NCBI

187 

Chen J, Xie JJ, Jin MY, Gu YT, Wu CC, Guo WJ, Yan YZ, Zhang ZJ, Wang JL, Zhang XL, et al: Sirt6 overexpression suppresses senescence and apoptosis of nucleus pulposus cells by inducing autophagy in a model of intervertebral disc degeneration. Cell Death Dis. 9:562018. View Article : Google Scholar : PubMed/NCBI

188 

Shan L, Wang F, Zhai D, Meng X, Liu J and Lv X: Matrix metalloproteinases induce extracellular matrix degradation through various pathways to alleviate hepatic fibrosis. Biomed Pharmacother. 161:1144722023. View Article : Google Scholar : PubMed/NCBI

189 

Valenti MT, Dalle Carbonare L, Zipeto D and Mottes M: Control of the autophagy pathway in osteoarthritis: Key regulators, therapeutic targets and therapeutic strategies. Int J Mol Sci. 22:27002021. View Article : Google Scholar : PubMed/NCBI

190 

Ryter SW, Cloonan SM and Choi AM: Autophagy: A critical regulator of cellular metabolism and homeostasis. Mol Cells. 36:7–16. 2013. View Article : Google Scholar : PubMed/NCBI

191 

Mu W and Wang Z, Ma C, Jiang Y, Zhang N, Hu K, Li L and Wang Z: Metformin promotes the proliferation and differentiation of murine preosteoblast by regulating the expression of sirt6 and oct4. Pharmacol Res. 129:462–474. 2018. View Article : Google Scholar

192 

Yang M, Peng Y, Liu W, Zhou M, Meng Q and Yuan C: Sirtuin 2 expression suppresses oxidative stress and senescence of nucleus pulposus cells through inhibition of the p53/p21 pathway. Biochem Biophys Res Commun. 513:616–622. 2019. View Article : Google Scholar : PubMed/NCBI

193 

Tang X, Chen XF, Wang NY, Wang XM, Liang ST, Zheng W, Lu YB, Zhao X, Hao DL, Zhang ZQ, et al: SIRT2 acts as a cardioprotective deacetylase in pathological cardiac hypertrophy. Circulation. 136:2051–2067. 2017. View Article : Google Scholar : PubMed/NCBI

194 

Dutta S, Shah RB, Singhal S, Dutta SB, Bansal S, Sinha S and Haque M: Metformin: A review of potential mechanism and therapeutic utility beyond diabetes. Drug Des Devel Ther. 17:1907–1932. 2023. View Article : Google Scholar : PubMed/NCBI

195 

Yanovski JA, Krakoff J, Salaita CG, McDuffie JR, Kozlosky M, Sebring NG, Reynolds JC, Brady SM and Calis KA: Effects of metformin on body weight and body composition in obese insulin-resistant children: A randomized clinical trial. Diabetes. 60:477–485. 2011. View Article : Google Scholar : PubMed/NCBI

196 

Seifarth C, Schehler B and Schneider HJ: Effectiveness of metformin on weight loss in non-diabetic individuals with obesity. Exp Clin Endocrinol Diabetes. 121:27–31. 2013.

197 

Piskovatska V, Storey KB, Vaiserman AM and Lushchak O: The use of metformin to increase the human healthspan. Adv Exp Med Biol. 1260:319–332. 2020. View Article : Google Scholar : PubMed/NCBI

198 

Valencia WM, Palacio A, Tamariz L and Florez H: Metformin and ageing: Improving ageing outcomes beyond glycaemic control. Diabetologia. 60:1630–1638. 2017. View Article : Google Scholar : PubMed/NCBI

199 

Espinoza SE, Musi N, Wang CP, Michalek J, Orsak B, Romo T, Powers B, Conde A, Moris M, Bair-Kelps D, et al: Rationale and study design of a randomized clinical trial of metformin to prevent frailty in older adults with prediabetes. J Gerontol A Biol Sci Med Sci. 75:102–109. 2020. View Article : Google Scholar :

200 

Kulkarni AS, Brutsaert EF, Anghel V, Zhang K, Bloomgarden N, Pollak M, Mar JC, Hawkins M, Crandall JP and Barzilai N: Metformin regulates metabolic and nonmetabolic pathways in skeletal muscle and subcutaneous adipose tissues of older adults. Aging Cell. 17:e127232018. View Article : Google Scholar : PubMed/NCBI

201 

Wang C, Chen B, Feng Q, Nie C and Li T: Clinical perspectives and concerns of metformin as an anti-aging drug. Aging Med (Milton). 3:266–275. 2020. View Article : Google Scholar

202 

World's first anti-aging TAME trial gets green-light-Longevity. Technology. https://www.longevity.technology/worlds-first-anti-aging-trial-gets-green-light/. Accessed July 1, 2020

203 

American Diabetes Association: Erratum: Standards of Care in diabetes-2023 abridged for primary care providers. Clin diabetes. 2023.41:4–31. View Article : Google Scholar

Clin Diabetes. 41:3282023. View Article : Google Scholar

204 

Sun R, Feng J and Wang J: Underlying mechanisms and treatment of cellular senescence-induced biological barrier interruption and related diseases. Aging Dis. 15:612–639. 2024. View Article : Google Scholar :

205 

Zhao JY, Sheng XL, Li CJ, Qin T, He RD, Dai GY, Cao Y, Lu HB, Duan CY and Hu JZ: Metformin promotes angiogenesis and functional recovery in aged mice after spinal cord injury by adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway. Neural Regen Res. 18:1553–1562. 2023. View Article : Google Scholar :

206 

Chen Q, Xie D, Yao Q and Yang L: Effect of metformin on locomotor function recovery in rat spinal cord injury model: A meta-analysis. Oxid Med Cell Longev. 2021:19480032021. View Article : Google Scholar : PubMed/NCBI

207 

Chao-Yang G, Peng C and Hai-Hong Z: Roles of NLRP3 inflammasome in intervertebral disc degeneration. Osteoarthritis Cartilage. 29:793–801. 2021. View Article : Google Scholar : PubMed/NCBI

208 

Vergroesen PP, Kingma I, Emanuel KS, Hoogendoorn RJ, Welting TJ, van Royen BJ, van Dieën JH and Smit TH: Mechanics and biology in intervertebral disc degeneration: a vicious circle. Osteoarthritis Cartilage. 23:1057–1070. 2015. View Article : Google Scholar : PubMed/NCBI

209 

Chen WK, Yu XH, Yang W, Wang C, He WS, Yan YG, Zhang J and Wang WJ: lncRNAs: Novel players in intervertebral disc degeneration and osteoarthritis. Cell Prolif. 50:e123132017. View Article : Google Scholar

210 

Fujiwara A, Lim TH, An HS, Tanaka N, Jeon CH, Andersson GB and Haughton VM: The effect of disc degeneration and facet joint osteoarthritis on the segmental flexibility of the lumbar spine. Spine (Phila Pa 1976). 25:3036–3044. 2000. View Article : Google Scholar

211 

Fine N, Lively S, Séguin CA, Perruccio AV, Kapoor M and Rampersaud R: Intervertebral disc degeneration and osteoarthritis: A common molecular disease spectrum. Nat Rev Rheumatol. 19:136–152. 2023. View Article : Google Scholar : PubMed/NCBI

212 

Lyu FJ, Cui H, Pan H, Mc Cheung K, Cao X, Iatridis JC and Zheng Z: Painful intervertebral disc degeneration and inflammation: from laboratory evidence to clinical interventions. Bone Res. 9:72021. View Article : Google Scholar : PubMed/NCBI

213 

Mojtahedzadeh M, Jafarieh A, Najafi A, Khajavi MR and Khalili N: Comparison of metformin and insulin in the control of hyperglycaemia in non-diabetic critically ill patients. Endokrynol Pol. 63:206–211. 2012.PubMed/NCBI

214 

Farkhondeh T, Amirabadizadeh A, Aramjoo H, Llorens S, Roshanravan B, Saeedi F, Talebi M, Shakibaei M and Samarghandian S: Impact of metformin on cancer biomarkers in non-diabetic cancer patients: A systematic review and meta-analysis of clinical trials. Curr Oncol. 28:1412–1423. 2021. View Article : Google Scholar : PubMed/NCBI

215 

Ko KP, Ma SH, Yang JJ, Hwang Y, Ahn C, Cho YM, Noh DY, Park BJ, Han W and Park SK: Metformin intervention in obese non-diabetic patients with breast cancer: Phase II randomized, double-blind, placebo-controlled trial. Breast Cancer Res Treat. 153:361–370. 2015. View Article : Google Scholar : PubMed/NCBI

216 

Lalau JD, Arnouts P, Sharif A and De Broe ME: Metformin and other antidiabetic agents in renal failure patients. Kidney Int. 87:308–322. 2015. View Article : Google Scholar

217 

Cetin M and Sahin S: Microparticulate and nanoparticulate drug delivery systems for metformin hydrochloride. Drug Deliv. 23:2796–2805. 2016. View Article : Google Scholar

218 

Adikwu MU, Yoshikawa Y and Takada K: Bioadhesive delivery of metformin using prosopis gum with antidiabetic potential. Biol Pharm Bull. 26:662–666. 2003. View Article : Google Scholar : PubMed/NCBI

219 

Varde NK and Pack DW: Microspheres for controlled release drug delivery. Expert Opin Biol Ther. 4:35–51. 2004. View Article : Google Scholar

220 

Alexis F, Pridgen EM, Langer R and Farokhzad OC: Nanoparticle technologies for cancer therapy. Handb Exp Pharmacol. 55–86. 2010. View Article : Google Scholar : PubMed/NCBI

221 

Feng Y, Egan B and Wang J: Genetic factors in intervertebral disc degeneration. Genes Dis. 3:178–185. 2016. View Article : Google Scholar : PubMed/NCBI

222 

Cosamalón-Gan I, Cosamalón-Gan T, Mattos-Piaggio G, Villar-Suárez V, García-Cosamalón J and Vega-Álvarez JA: Inflammation in the intervertebral disc herniation. Neurocirugia (Astur : Engl Ed). 32:21–35. 2021.In English, Spanish. View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Yang W, Yang Y, Wang Y, Gao Z, Zhang J, Gao W, Chen Y, Lu Y, Wang H, Zhou L, Zhou L, et al: Metformin prevents the onset and progression of intervertebral disc degeneration: New insights and potential mechanisms (Review). Int J Mol Med 54: 71, 2024.
APA
Yang, W., Yang, Y., Wang, Y., Gao, Z., Zhang, J., Gao, W. ... Tao, H. (2024). Metformin prevents the onset and progression of intervertebral disc degeneration: New insights and potential mechanisms (Review). International Journal of Molecular Medicine, 54, 71. https://doi.org/10.3892/ijmm.2024.5395
MLA
Yang, W., Yang, Y., Wang, Y., Gao, Z., Zhang, J., Gao, W., Chen, Y., Lu, Y., Wang, H., Zhou, L., Wang, Y., Li, J., Tao, H."Metformin prevents the onset and progression of intervertebral disc degeneration: New insights and potential mechanisms (Review)". International Journal of Molecular Medicine 54.2 (2024): 71.
Chicago
Yang, W., Yang, Y., Wang, Y., Gao, Z., Zhang, J., Gao, W., Chen, Y., Lu, Y., Wang, H., Zhou, L., Wang, Y., Li, J., Tao, H."Metformin prevents the onset and progression of intervertebral disc degeneration: New insights and potential mechanisms (Review)". International Journal of Molecular Medicine 54, no. 2 (2024): 71. https://doi.org/10.3892/ijmm.2024.5395
Copy and paste a formatted citation
x
Spandidos Publications style
Yang W, Yang Y, Wang Y, Gao Z, Zhang J, Gao W, Chen Y, Lu Y, Wang H, Zhou L, Zhou L, et al: Metformin prevents the onset and progression of intervertebral disc degeneration: New insights and potential mechanisms (Review). Int J Mol Med 54: 71, 2024.
APA
Yang, W., Yang, Y., Wang, Y., Gao, Z., Zhang, J., Gao, W. ... Tao, H. (2024). Metformin prevents the onset and progression of intervertebral disc degeneration: New insights and potential mechanisms (Review). International Journal of Molecular Medicine, 54, 71. https://doi.org/10.3892/ijmm.2024.5395
MLA
Yang, W., Yang, Y., Wang, Y., Gao, Z., Zhang, J., Gao, W., Chen, Y., Lu, Y., Wang, H., Zhou, L., Wang, Y., Li, J., Tao, H."Metformin prevents the onset and progression of intervertebral disc degeneration: New insights and potential mechanisms (Review)". International Journal of Molecular Medicine 54.2 (2024): 71.
Chicago
Yang, W., Yang, Y., Wang, Y., Gao, Z., Zhang, J., Gao, W., Chen, Y., Lu, Y., Wang, H., Zhou, L., Wang, Y., Li, J., Tao, H."Metformin prevents the onset and progression of intervertebral disc degeneration: New insights and potential mechanisms (Review)". International Journal of Molecular Medicine 54, no. 2 (2024): 71. https://doi.org/10.3892/ijmm.2024.5395
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