Tanshinone‑IIA attenuates the deleterious effects of oxidative stress in osteoporosis through the NF‑κB signaling pathway Retraction in /10.3892/mmr.2023.13140

Zhu,Shaowen; Wei,Wanfu; Liu,Zhiwei; Yang,Yang; Jia,Haobo

doi:10.3892/mmr.2018.8741

Tanshinone‑IIA attenuates the deleterious effects of oxidative stress in osteoporosis through the NF‑κB signaling pathway

Retraction in: /10.3892/mmr.2023.13140

Authors:
- Shaowen Zhu
- Wanfu Wei
- Zhiwei Liu
- Yang Yang
- Haobo Jia
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Affiliations: Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China, Department of Orthopedics, Tianjin Hospital, Tianjin 300211, P.R. China, Basic Medicine Institution, Public Health Center, Peking University, Beijing 100871, P.R. China
Published online on: March 14, 2018 https://doi.org/10.3892/mmr.2018.8741
Pages: 6969-6976
Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osteoclasts are responsible for bone resorption caused by bone microstructural damage and bonerelated disorders. Evidence shows that tanshinone IIA (Tan‑IIA), a traditional Chinese medicine, is used clinically as a drug for the treatment of cardiovascular and cerebrovascular diseases. However, the efficacy and mechanism underlying the effect of Tan‑IIA on the viability of osteoclasts remain to be fully elucidated. The present study investigated the therapeutic effects of Tan‑IIA on osteoblast differentiation and oxidative stress in vitro and in vivo. Cell viability was analyzed and oxidative stress was examined in the osteoblasts. Wnt1sw/sw mice were used to investigate the therapeutic effects of Tan‑IIA on spontaneous tibia fractures and severe osteopenia. The bone strength, collagen and mineral were examined in the tibia. Osteoblast activity was also analyzed in the experimental mice. The Tan‑IIA‑induced differentiation of osteoclasts and the mechanism of action were investigated in osteocytes. The data showed that Tan‑IIA treatment improved cell viability. The data also demonstrated that Tan‑IIA decreased the levels of H2O2, accumulation of reactive oxygen species and apoptosis of osteoblasts. Tan‑IIA inhibited the deleterious outcomes triggered by oxidative stress. In addition, Tan‑IIA inhibited the activation of nuclear factor (NF)‑κB and its target genes, tumor necrosis factor (TNF)‑α, inducible nitric oxide synthase and cyclooxygenase 2, and increased the levels of TNF receptor‑associated factor 1 and inhibitor of apoptosis protein‑1/2 in the osteocytes. Furthermore, it was shown that Tan‑IIA reduced the propensity to fractures and severe osteopenia in mice with osteoporosis. Tan‑IIA also exhibited improved bone strength, mineral and collagen in the bone matrix of the experimental mice. It was found that the Tan‑IIA‑mediated benefits on osteoblast activity and function were through the NF‑κB signaling pathway. Taken together, the data obtained in the present study suggested that Tan‑IIA had protective effects against oxidative stress in osteoblastic differentiation in mice with osteoporosis by regulating the NF‑κB signaling pathway.

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1	Cornelius C, Koverech G, Crupi R, Di Paola R, Koverech A, Lodato F, Scuto M, Salinaro AT, Cuzzocrea S, Calabrese EJ and Calabrese V: Osteoporosis and alzheimer pathology: Role of cellular stress response and hormetic redox signaling in aging and bone remodeling. Front Pharmacol. 5:1202014. View Article : Google Scholar : PubMed/NCBI
2	Kondo T, Endo I and Matsumoto T: The pathology, diagnosis and therapy on osteoporosis. Nihon Rinsho. 72:1774–1779. 2014.(In Japanese). PubMed/NCBI
3	Scott LJ: Denosumab: A review of its use in postmenopausal women with osteoporosis. Drugs Aging. 31:555–576. 2014. View Article : Google Scholar : PubMed/NCBI
4	Yu S, Liu F, Cheng Z and Wang Q: Association between osteoporosis and benign paroxysmal positional vertigo: A systematic review. BMC Neurol. 14:1102014. View Article : Google Scholar : PubMed/NCBI
5	Henriksen K, Bollerslev J, Everts V and Karsdal MA: Osteoclast activity and subtypes as a function of physiology and pathology-implications for future treatments of osteoporosis. Endocr Rev. 32:31–63. 2011. View Article : Google Scholar : PubMed/NCBI
6	Sadat-Ali M, Al-Omran A, Al-Bakr W, Azam MQ, Tantawy A and Al-Othman A: Established osteoporosis and gaps in the management: Review from a teaching hospital. Ann Med Health Sci Res. 4:198–201. 2014. View Article : Google Scholar : PubMed/NCBI
7	Miyazaki T, Tokimura F and Tanaka S: A review of denosumab for the treatment of osteoporosis. Patient Prefer Adherence. 8:463–471. 2014. View Article : Google Scholar : PubMed/NCBI
8	Li F, Han G and Wu K: Tanshinone IIA alleviates the AD phenotypes in APP and PS1 transgenic mice. Biomed Res Int. 2016:76318012016.PubMed/NCBI
9	Kim EO, Kang SE, Im CR, Lee JH, Ahn KS, Yang WM, Um JY, Lee SG and Yun M: Tanshinone IIA induces TRAIL sensitization of human lung cancer cells through selective ER stress induction. Int J Oncol. 48:2205–2212. 2016. View Article : Google Scholar : PubMed/NCBI
10	Su CC and Chiu TL: Tanshinone IIA decreases the protein expression of EGFR and IGFR blocking the PI3K/Akt/mTOR pathway in gastric carcinoma AGS cells both in vitro and in vivo. Oncol Rep. 36:1173–1179. 2016. View Article : Google Scholar : PubMed/NCBI
11	Jiang Q, Lu W, Yang K, Hadadi C, Fu X, Chen Y, Yun X, Zhang J, Li M, Xu L, et al: Sodium tanshinone IIA sulfonate inhibits hypoxia-induced enhancement of SOCE in pulmonary arterial smooth muscle cells via the PKG-PPAR-γ signaling axis. Am J Physiol Cell Physiol. 311:C136–C149. 2016. View Article : Google Scholar : PubMed/NCBI
12	Mao C, Zhang Y, Cao L, Shao H, Wang L, Zhu L and Xu Z: The effect of tanshinone IIA on the cardiovascular system in ovine fetus in utero. AM J Chin Med. 37:1031–1044. 2009. View Article : Google Scholar : PubMed/NCBI
13	Ma S, Liu W, Liu P, Liu J, Chen L and Qin C: Tanshinone IIA treatment alleviated the rat gingival connective tissue overgrowth induced by cyclosporine A. J Periodontal Res. 51:567–576. 2016. View Article : Google Scholar : PubMed/NCBI
14	Li DC, Bao XQ, Sun H and Zhang D: Research progress in the study of protective effect of tanshinone IIA on cerebral ischemic stroke. Yao Xue Xue Bao. 50:635–639. 2015.(In Chinese). PubMed/NCBI
15	Ouyang DS, Huang WH, Chen D, Zhang W, Tan ZR, Peng JB, Wang YC, Guo Y, Hu DL, Xiao J and Chen Y: Kinetics of cytochrome P450 enzymes for metabolism of sodium tanshinone IIA sulfonate in vitro. Chin Med. 11:112016. View Article : Google Scholar : PubMed/NCBI
16	Bai Y, Zhang L, Fang X and Yang Y: Tanshinone IIA enhances chemosensitivity of colon cancer cells by suppressing nuclear factor-κB. Exp Ther Med. 11:1085–1089. 2016. View Article : Google Scholar : PubMed/NCBI
17	Kurian GA, Rajagopal R, Vedantham S and Rajesh M: The role of oxidative stress in myocardial ischemia and reperfusion injury and remodeling: Revisited. Oxid Med Cell Longev. 2016:16564502016. View Article : Google Scholar : PubMed/NCBI
18	Saito M: On ‘2015 guidelines for prevention and treatment of osteoporosis’. The mechanism of bone fragility. Clin Calcium. 25:1301–1306. 2015.(In Japanese). PubMed/NCBI
19	Koga T and Takayanagi H: On ‘2015 guidelines for prevention and treatment of osteoporosis’. Cellular mechanism and etiology of osteoporosis. Clin Calcium. 25:1293–1300. 2015.(In Japanese). PubMed/NCBI
20	Wu Q, Zhong ZM, Pan Y, Zeng JH, Zheng S, Zhu SY and Chen J: Advanced oxidation protein products as a novel marker of oxidative stress in postmenopausal osteoporosis. Med Sci. 21:2428–2432. 2015.
21	Yang YH, Li B, Zheng XF, Chen JW, Chen K, Jiang SD and Jiang LS: Oxidative damage to osteoblasts can be alleviated by early autophagy through the endoplasmic reticulum stress pathway-implications for the treatment of osteoporosis. Free Radic Biol Med. 77:10–20. 2014. View Article : Google Scholar : PubMed/NCBI
22	Spilmont M, Leotoing L, Davicco MJ, Lebecque P, Mercier S, Miot-Noirault E, Pilet P, Rios L, Wittrant Y and Coxam V: Pomegranate and its derivatives can improve bone health through decreased inflammation and oxidative stress in an animal model of postmenopausal osteoporosis. Eur J Nutr. 53:1155–1164. 2014. View Article : Google Scholar : PubMed/NCBI
23	Wilson C: Bone: Oxidative stress and osteoporosis. Nat Rev Endocrinol. 10:32014. View Article : Google Scholar
24	Couzin-Frankel J: National Institutes of Health. Needed: More females in animal and cell studies. Science. 344:6792014. View Article : Google Scholar : PubMed/NCBI
25	Kushwaha P, Khedgikar V, Ahmad N, Karvande A, Gautam J, Kumar P, Maurya R and Trivedi R: A neoflavonoid dalsissooal isolated from heartwood of Dalbergia sissoo Roxb. has bone forming effects in mice model for osteoporosis. Eur J Pharmacol. 788:65–74. 2016. View Article : Google Scholar : PubMed/NCBI
26	Shum LC, White NS, Nadtochiy SM, Bentley KL, Brookes PS, Jonason JH and Eliseev RA: Cyclophilin D knock-out mice show enhanced resistance to osteoporosis and to metabolic changes observed in aging bone. PLoS One. 11:e01557092016. View Article : Google Scholar : PubMed/NCBI
27	Gartland A, Rumney RM, Dillon JP and Gallagher JA: Isolation and culture of human osteoblasts. Methods Mol Biol. 806:337–355. 2012. View Article : Google Scholar : PubMed/NCBI
28	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
29	Wai-Hoe L, Wing-Seng L, Ismail Z and Lay-Harn G: SDS-PAGE-based quantitative assay for screening of kidney stone disease. Biol Proced Online. 11:pp. 145–160. 2009; View Article : Google Scholar : PubMed/NCBI
30	Williams EL, White K and Oreffo RO: Isolation and enrichment of Stro-1 immunoselected mesenchymal stem cells from adult human bone marrow. Methods Mol Biol. 1035:67–73. 2013. View Article : Google Scholar : PubMed/NCBI
31	Elsafadi M, Manikandan M, Dawud RA, Alajez NM, Hamam R, Alfayez M, Kassem M, Aldahmash A and Mahmood A: Transgelin is a TGFβ-inducible gene that regulates osteoblastic and adipogenic differentiation of human skeletal stem cells through actin cytoskeleston organization. Cell Death Dis. 7:e23212016. View Article : Google Scholar : PubMed/NCBI
32	Lambert MF, Cook JV, Roelant E, Bradshaw C, Foy R and Eccles MP: Feasibility of applying review criteria for depression and osteoporosis national guidance in primary care. Prim Health Care Res Dev. 15:396–405. 2014. View Article : Google Scholar : PubMed/NCBI
33	Ghosh M and Majumdar SR: Antihypertensive medications, bone mineral density and fractures: A review of old cardiac drugs that provides new insights into osteoporosis. Endocrine. 46:397–405. 2014. View Article : Google Scholar : PubMed/NCBI
34	Sanchez-Rodriguez MA, Ruiz-Ramos M, Correa-Muñoz E and Mendoza-Núñez VM: Oxidative stress as a risk factor for osteoporosis in elderly Mexicans as characterized by antioxidant enzymes. BMC Musculoskelet Disord. 8:1242007. View Article : Google Scholar : PubMed/NCBI
35	Chavan SN, More U, Mulgund S, Saxena V and Sontakke AN: Effect of supplementation of vitamin C and E on oxidative stress in osteoporosis. Indian J Clin Biochem. 22:101–105. 2007. View Article : Google Scholar : PubMed/NCBI
36	Yin H, Shi ZG, Yu YS, Hu J, Wang R, Luan ZP and Guo DH: Protection against osteoporosis by statins is linked to a reduction of oxidative stress and restoration of nitric oxide formation in aged and ovariectomized rats. Eur J Pharmacol. 674:200–206. 2012. View Article : Google Scholar : PubMed/NCBI
37	Baek KH, Oh KW, Lee WY, Lee SS, Kim MK, Kwon HS, Rhee EJ, Han JH, Song KH, Cha BY, et al: Association of oxidative stress with postmenopausal osteoporosis and the effects of hydrogen peroxide on osteoclast formation in human bone marrow cell cultures. Calcif Tissue Int. 87:226–235. 2010. View Article : Google Scholar : PubMed/NCBI
38	Cervellati C, Bonaccorsi G, Cremonini E, Romani A, Fila E, Castaldini MC, Ferrazzini S, Giganti M and Massari L: Oxidative stress and bone resorption interplay as a possible trigger for postmenopausal osteoporosis. Biomed Res Int. 2014:5695632014. View Article : Google Scholar : PubMed/NCBI
39	Yilmaz N and Eren E: Homocysteine oxidative stress and relation to bone mineral density in post-menopausal osteoporosis. Aging Clin Exp Res. 21:353–357. 2009. View Article : Google Scholar : PubMed/NCBI
40	Puntmann VO, Taylor PC and Mayr M: Coupling vascular and myocardial inflammatory injury into a common phenotype of cardiovascular dysfunction: Systemic inflammation and aging-a mini-review. Gerontology. 57:295–303. 2011. View Article : Google Scholar : PubMed/NCBI
41	Ramachandran A, Jha S and Lefer DJ: Review paper: Pathophysiology of myocardial reperfusion injury: The role of genetically engineered mouse models. Vet Pathol. 45:698–706. 2008. View Article : Google Scholar : PubMed/NCBI
42	Lee WS, Lee EG, Sung MS, Choi YJ and Yoo WH: Atorvastatin inhibits osteoclast differentiation by suppressing NF-κB and MAPK signaling during IL-1β-induced osteoclastogenesis. Korean J Intern Med. Mar 28–2017.(Epub ahead of print).
43	Handzlik-Orlik G, Holecki M, Wilczynski K and Dulawa J: Osteoporosis in liver disease: Pathogenesis and management. Ther Adv Endocrinol Metab. 7:128–135. 2016. View Article : Google Scholar : PubMed/NCBI
44	Kim IH, Chung MY, Shin JY and Han D: Protective effects of black hoof medicinal mushroom from Κorea, Phellinus linteus (higher basidiomycetes), on osteoporosis in vitro and in vivo. Int J Med Mushrooms. 18:39–47. 2016. View Article : Google Scholar : PubMed/NCBI