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Article Open Access

MicroRNA‑338‑3p regulates age‑associated osteoporosis via targeting PCSK5

  • Authors:
    • Jie Tong
    • Min Zhang
    • Xia Li
    • Guohai Ren
  • View Affiliations / Copyright

    Affiliations: Department of Orthopedics, Affiliated Hospital of Jianghan University, Wuhan, Hubei 430015, P.R. China, Emergency Department, Wuhan Hospital of Traditional Chinese and Western Medicine, Wuhan, Hubei 430022, P.R. China, Department of Ophthalmology and Otorhinolaryngology, Affiliated Hospital of Jianghan University, Wuhan, Hubei 430015, P.R. China
    Copyright: © Tong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 136
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    Published online on: December 13, 2020
       https://doi.org/10.3892/mmr.2020.11775
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Abstract

Bone loss is a disease that is highly associated with aging. This deleterious health condition has become a public concern worldwide, and there is an urgent need to discover more novel therapeutic strategies for the development of age‑associated osteoporosis. The present study aimed to explore the association between proprotein convertase subtilisin/kexin type 5 (PCSK5) and microRNA(miR)‑338‑3p in bone‑formation and bone‑loss processes. Western blotting assay and reverse transcription‑quantitative PCR were employed to analyze PCSK5 and miR‑338‑3p expression levels in bone mesenchymal stem cells (BMSCs). Dual‑luciferase reporter and RNA pull‑down assays were used to determine the target. For osteoblastic differentiation verification, alkaline phosphatase activity, osteocalcin secretion detection, bone formation‑related indicators (osterix, runt‑related gene 2, osteopontin and bone sialoprotein), hematoxylin and eosin staining and Alizarin Red S staining were performed. The findings of the present study indicated that the expression level of PCSK5 was higher in BMSCs from young rat samples, whereas the expression level of miR‑338‑3p was higher in BMSCs from samples of old rats. Experimental results also revealed that unlike miR‑338‑3p, downregulation of PCSK5 inhibited osteoblastic differentiation and osteogenesis by inhibiting alkaline phosphatase, osteocalcin, osterix, runt‑related transcription factor 2, osteopontin, bone sialoprotein and mineralized nodule formation. Overall, the results suggested that miR‑338‑3p could suppress age‑associated osteoporosis by regulating PCSK5.
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1 

Kiernan J, Hu S, Grynpas MD, Davies JE and Stanford WL: Systemic Mesenchymal Stromal Cell Transplantation Prevents Functional Bone Loss in a Mouse Model of Age-Related Osteoporosis. Stem Cells Transl Med. 5:683–693. 2016. View Article : Google Scholar : PubMed/NCBI

2 

Compston JE, McClung MR and Leslie WD: Osteoporosis. Lancet. 393:364–376. 2019. View Article : Google Scholar : PubMed/NCBI

3 

Prockop DJ: Marrow stromal cells as stem cells for nonhematopoietic tissues. Science. 276:71–74. 1997. View Article : Google Scholar : PubMed/NCBI

4 

Chen Q, Shou P, Zheng C, Jiang M, Cao G, Yang Q, Cao J, Xie N, Velletri T, Zhang X, et al: Fate decision of mesenchymal stem cells: Adipocytes or osteoblasts? Cell Death Differ. 23:1128–1139. 2016. View Article : Google Scholar : PubMed/NCBI

5 

Tae JY, Lee H, Lee H, Ko Y and Park JB: Osteogenic potential of cell spheroids composed of varying ratios of gingiva-derived and bone marrow stem cells using concave microwells. Exp Ther Med. 16:2287–2294. 2018.PubMed/NCBI

6 

Almalki SG and Agrawal DK: Key transcription factors in the differentiation of mesenchymal stem cells. Differentiation. 92:41–51. 2016. View Article : Google Scholar : PubMed/NCBI

7 

He S, Yang S, Zhang Y, Li X, Gao D, Zhong Y, Cao L, Ma H, Liu Y, Li G, et al: LncRNA ODIR1 inhibits osteogenic differentiation of hUC-MSCs through the FBXO25/H2BK120ub/H3K4me3/OSX axis. Cell Death Dis. 10:9472019. View Article : Google Scholar : PubMed/NCBI

8 

Yin Q, Wang J, Fu Q, Gu S and Rui Y: CircRUNX2 through has-miR-203 regulates RUNX2 to prevent osteoporosis. J Cell Mol Med. 22:6112–6121. 2018. View Article : Google Scholar : PubMed/NCBI

9 

Li CJ, Cheng P, Liang MK, Chen YS, Lu Q, Wang JY, Xia ZY, Zhou HD, Cao X, Xie H, et al: MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation. J Clin Invest. 125:1509–1522. 2015. View Article : Google Scholar : PubMed/NCBI

10 

Moerman EJ, Teng K, Lipschitz DA and Lecka-Czernik B: Aging activates adipogenic and suppresses osteogenic programs in mesenchymal marrow stroma/stem cells: The role of PPAR-gamma2 transcription factor and TGF-beta/BMP signaling pathways. Aging Cell. 3:379–389. 2004. View Article : Google Scholar : PubMed/NCBI

11 

Wu J, Zhang W, Ran Q, Xiang Y, Zhong JF, Li SC and Li Z: The differentiation balance of bone marrow mesenchymal stem cells is crucial to hematopoiesis. Stem Cells Int. 2018:15401482018. View Article : Google Scholar : PubMed/NCBI

12 

Yu B and Wang CY: Osteoporosis: The result of an ‘aged’ bone microenvironment. Trends Mol Med. 22:641–644. 2016. View Article : Google Scholar : PubMed/NCBI

13 

Khosla S and Hofbauer LC: Osteoporosis treatment: Recent developments and ongoing challenges. Lancet Diabetes Endocrinol. 5:898–907. 2017. View Article : Google Scholar : PubMed/NCBI

14 

Cheung CL, Xiao SM and Kung AW: Genetic epidemiology of age-related osteoporosis and its clinical applications. Nat Rev Rheumatol. 6:507–517. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Carey JJ, Lewiecki EM, Blank RD, Shuhart CR and Buehring B: Treatment of low bone density or osteoporosis to prevent fractures in men and women. Ann Intern Med. 167:9012017. View Article : Google Scholar : PubMed/NCBI

16 

Lorentzon M and Cummings SR: Osteoporosis: The evolution of a diagnosis. J Intern Med. 277:650–661. 2015. View Article : Google Scholar : PubMed/NCBI

17 

Sànchez-Riera L, Carnahan E, Vos T, Veerman L, Norman R, Lim SS, Hoy D, Smith E, Wilson N, Nolla JM, et al: The global burden attributable to low bone mineral density. Ann Rheum Dis. 73:1635–1645. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Turpeinen H, Ortutay Z and Pesu M: Genetics of the first seven proprotein convertase enzymes in health and disease. Curr Genomics. 14:453–467. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Osathanon T, Manokawinchoke J, Sa-Ard-Iam N, Mahanonda R, Pavasant P and Suwanwela J: Jagged1 promotes mineralization in human bone-derived cells. Arch Oral Biol. 99:134–140. 2019. View Article : Google Scholar : PubMed/NCBI

20 

McPherron AC, Lawler AM and Lee SJ: Regulation of anterior/posterior patterning of the axial skeleton by growth/differentiation factor 11. Nat Genet. 22:260–264. 1999. View Article : Google Scholar : PubMed/NCBI

21 

Liu H, Sun Q, Wan C, Li L, Zhang L and Chen Z: MicroRNA-338-3p regulates osteogenic differentiation of mouse bone marrow stromal stem cells by targeting Runx2 and Fgfr2. J Cell Physiol. 229:1494–1502. 2014. View Article : Google Scholar : PubMed/NCBI

22 

Zhang XH, Geng GL, Su B, Liang CP, Wang F and Bao JC: MicroRNA-338-3p inhibits glucocorticoid-induced osteoclast formation through RANKL targeting. Genet Mol Res. 15:gmr.15037674. 2016.

23 

Niu D, Gong Z, Sun X, Yuan J, Zheng T, Wang X, Fan X, Mao Y, Liu X, Tang B, et al: miR-338-3p regulates osteoclastogenesis via targeting IKKβ gene. In Vitro Cell Dev Biol Anim. 55:243–251. 2019. View Article : Google Scholar

24 

Benisch P, Schilling T, Klein-Hitpass L, Frey SP, Seefried L, Raaijmakers N, Krug M, Regensburger M, Zeck S, Schinke T, et al: The transcriptional profile of mesenchymal stem cell populations in primary osteoporosis is distinct and shows overexpression of osteogenic inhibitors. PLoS One. 7:e451422012. View Article : Google Scholar : PubMed/NCBI

25 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

26 

Li Y, Zheng F, Xiao X, Xie F, Tao D, Huang C, Liu D, Wang M, Wang L, Zeng F, et al: CircHIPK3 sponges miR-558 to suppress heparanase expression in bladder cancer cells. EMBO Rep. 18:1646–1659. 2017. View Article : Google Scholar : PubMed/NCBI

27 

Szumska D, Pieles G, Essalmani R, Bilski M, Mesnard D, Kaur K, Franklyn A, El Omari K, Jefferis J, Bentham J, et al: VACTERL/caudal regression/Currarino syndrome-like malformations in mice with mutation in the proprotein convertase Pcsk5. Genes Dev. 22:1465–1477. 2008. View Article : Google Scholar : PubMed/NCBI

28 

Hoac B, Susan-Resiga D, Essalmani R, Marcinkiweicz E, Seidah NG and McKee MD: Osteopontin as a novel substrate for the proprotein convertase 5/6 (PCSK5) in bone. Bone. 107:45–55. 2018. View Article : Google Scholar : PubMed/NCBI

29 

Marie PJ: Targeting integrins to promote bone formation and repair. Nat Rev Endocrinol. 9:288–295. 2013. View Article : Google Scholar : PubMed/NCBI

30 

Eastell R, O'Neill TW, Hofbauer LC, Langdahl B, Reid IR, Gold DT and Cummings SR: Postmenopausal osteoporosis. Nat Rev Dis Primers. 2:160692016. View Article : Google Scholar : PubMed/NCBI

31 

Long H, Sun B, Cheng L, Zhao S, Zhu Y, Zhao R and Zhu J: miR-139-5p represses BMSC osteogenesis via targeting Wnt/β-catenin signaling pathway. DNA Cell Biol. 36:715–724. 2017. View Article : Google Scholar : PubMed/NCBI

32 

Zhang S, Liu Y, Zheng Z, Zeng X, Liu D, Wang C and Ting K: MicroRNA-223 suppresses osteoblast differentiation by inhibiting DHRS3. Cell Physiol Biochem. 47:667–679. 2018. View Article : Google Scholar : PubMed/NCBI

33 

Fu L, Liu H and Lei W: MiR-596 inhibits osteoblastic differentiation and cell proliferation by targeting Smad3 in steroid-induced osteonecrosis of femoral head. J Orthop Surg Res. 15:1732020. View Article : Google Scholar : PubMed/NCBI

34 

Zhou S, Qian B, Wang L, Zhang C, Hogan MV and Li H: Altered bone-regulating myokine expression in skeletal muscle Of Duchenne muscular dystrophy mouse models. Muscle Nerve. 58:573–582. 2018. View Article : Google Scholar : PubMed/NCBI

35 

Bartold M, Gronthos S, Haynes D and Ivanovski S: Mesenchymal stem cells and biologic factors leading to bone formation. J Clin Periodontol. 46 (Suppl 21):12–32. 2019. View Article : Google Scholar : PubMed/NCBI

36 

Alcorta-Sevillano N, Macías I, Rodríguez CI and Infante A: Crucial role of Lamin A/C in the migration and differentiation of MSCs in bone. Cells. 9:E13302020. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Tong J, Zhang M, Li X and Ren G: MicroRNA‑338‑3p regulates age‑associated osteoporosis via targeting PCSK5. Mol Med Rep 23: 136, 2021.
APA
Tong, J., Zhang, M., Li, X., & Ren, G. (2021). MicroRNA‑338‑3p regulates age‑associated osteoporosis via targeting PCSK5. Molecular Medicine Reports, 23, 136. https://doi.org/10.3892/mmr.2020.11775
MLA
Tong, J., Zhang, M., Li, X., Ren, G."MicroRNA‑338‑3p regulates age‑associated osteoporosis via targeting PCSK5". Molecular Medicine Reports 23.2 (2021): 136.
Chicago
Tong, J., Zhang, M., Li, X., Ren, G."MicroRNA‑338‑3p regulates age‑associated osteoporosis via targeting PCSK5". Molecular Medicine Reports 23, no. 2 (2021): 136. https://doi.org/10.3892/mmr.2020.11775
Copy and paste a formatted citation
x
Spandidos Publications style
Tong J, Zhang M, Li X and Ren G: MicroRNA‑338‑3p regulates age‑associated osteoporosis via targeting PCSK5. Mol Med Rep 23: 136, 2021.
APA
Tong, J., Zhang, M., Li, X., & Ren, G. (2021). MicroRNA‑338‑3p regulates age‑associated osteoporosis via targeting PCSK5. Molecular Medicine Reports, 23, 136. https://doi.org/10.3892/mmr.2020.11775
MLA
Tong, J., Zhang, M., Li, X., Ren, G."MicroRNA‑338‑3p regulates age‑associated osteoporosis via targeting PCSK5". Molecular Medicine Reports 23.2 (2021): 136.
Chicago
Tong, J., Zhang, M., Li, X., Ren, G."MicroRNA‑338‑3p regulates age‑associated osteoporosis via targeting PCSK5". Molecular Medicine Reports 23, no. 2 (2021): 136. https://doi.org/10.3892/mmr.2020.11775
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