Skip to main content

Advertisement

SpringerLink
Log in

RETRACTED ARTICLE: Overexpression of CAV3 facilitates bone formation via the Wnt signaling pathway in osteoporotic rats

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

This article was retracted on 11 March 2022

A Correction to this article was published on 18 September 2020

This article has been updated

Abstract

Purpose

Osteoporosis is a condition characterized by decreased bone density and bone strength, commonly observed among older individuals. Caveolin-3 (CAV3) is a principal structural protein of the caveolae membrane domains, which has been reported to participate in cell signaling as well as the maintenance of cell structure. The aim of the current study was to investigate the effects involved with the silencing of CAV3 on bone formation among osteoporotic rat models via the Wnt signaling pathway.

Methods

Osteoporosis was initially induced by means of ovariotomy among rat models in order to determine the expression of CAV3. Then, to confirm the specific function and mechanism of CAV3 from an osteoporosis perspective, the CAV3 expression vector was constructed and transfected into the osteoblasts of the osteoporotic rats. Afterward, the mRNA and protein expressions of CAV3, β-catenin, low-density lipoprotein receptor-related protein 5 (LRP5), T-cell factor (TCF), and Wnt3a in addition to cell proliferation and apoptosis were detected accordingly.

Results

Positive expression of CAV3 exhibited diminished levels in the bone tissues of osteoporotic rats. The osteoblasts of the osteoporotic rats treated with overexpressed CAV3 displayed elevated mRNA and protein expression levels of β-catenin, LRP5, TCF, and Wnt3a. Increased cell proliferation and decreased cell apoptosis were also observed, while the osteoblasts of the osteoporotic rats treated with si-CAV3 exhibited an opposite result.

Conclusion

Overexpressed CAV3 promotes bone formation and suppresses the osteoporosis progression via the activation of the Wnt signaling in rat models, suggesting CAV3 as a potential target biomarker in the treatment of osteoporosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

Change history

References

  1. E.M. Curtis, R.J. Moon, N.C. Harvey, C. Cooper, The impact of fragility fracture and approaches to osteoporosis risk assessment worldwide. Bone 104, 29–38 (2017)

    Article  Google Scholar 

  2. R. Baron, M. Kneissel, WNT signaling in bone homeostasis and disease: from human mutations to treatments. Nat. Med. 19(2), 179–192 (2013)

    Article  CAS  Google Scholar 

  3. S.W. Wade, C. Strader, L.A. Fitzpatrick, M.S. Anthony, C.D. O’Malley, Estimating prevalence of osteoporosis: examples from industrialized countries. Arch. Osteoporos. 9, 182 (2014)

    Article  CAS  Google Scholar 

  4. N.D. Zhang, T. Han, B.K. Huang, K. Rahman, Y.P. Jiang, H.T. Xu, L.P. Qin, H.L. Xin, Q.Y. Zhang, Y.M. Li, Traditional Chinese medicine formulas for the treatment of osteoporosis: Implication for antiosteoporotic drug discovery. J. Ethnopharmacol. 189, 61–80 (2016)

    Article  Google Scholar 

  5. K. Lippuner, The future of osteoporosis treatment - a research update. Swiss Med. Wkly 142, w13624 (2012)

    PubMed  Google Scholar 

  6. R. Yuan, S. Ma, X. Zhu, J. Li, Y. Liang, T. Liu, Y. Zhu, B. Zhang, S. Tan, H. Guo, S. Guan, P. Ao, G. Zhou, Core level regulatory network of osteoblast as molecular mechanism for osteoporosis and treatment. Oncotarget 7(4), 3692–3701 (2016)

    Article  Google Scholar 

  7. J. Cheng, C.R. Valdivia, R. Vaidyanathan, R.C. Balijepalli, M.J. Ackerman, J.C. Makielski, Caveolin-3 suppresses late sodium current by inhibiting nNOS-dependent S-nitrosylation of SCN5A. J. Mol. Cell. Cardiol. 61, 102–110 (2013)

    Article  CAS  Google Scholar 

  8. P. Nassoy, C. Lamaze, Stressing caveolae new role in cell mechanics. Trends Cell Biol. 22(7), 381–389 (2012)

    Article  Google Scholar 

  9. M. Maceckova, H. Martiskova, A. Koudelka, L. Kubala, A. Lojek, M. Pekarova, Bone marrow-derived macrophages exclusively expressed caveolin-2: the role of inflammatory activators and hypoxia. Immunobiology 220(11), 1266–1274 (2015)

    Article  CAS  Google Scholar 

  10. C. Niehrs, The complex world of WNT receptor signalling. Nat. Rev. Mol. Cell Biol. 13(12), 767–779 (2012)

    Article  CAS  Google Scholar 

  11. J.N. Anastas, R.T. Moon, WNT signalling pathways as therapeutic targets in cancer. Nat. Rev. Cancer 13(1), 11–26 (2013)

    Article  CAS  Google Scholar 

  12. D.G. Monroe, M.E. McGee-Lawrence, M.J. Oursler, J.J. Westendorf, Update on Wnt signaling in bone cell biology and bone disease. Gene 492(1), 1–18 (2012)

    Article  CAS  Google Scholar 

  13. G. Yuan, I. Regel, F. Lian, T. Friedrich, I. Hitkova, R.D. Hofheinz, P. Strobel, R. Langer, G. Keller, C. Rocken, W. Zimmermann, R.M. Schmid, M.P. Ebert, E. Burgermeister, WNT6 is a novel target gene of caveolin-1 promoting chemoresistance to epirubicin in human gastric cancer cells. Oncogene 32(3), 375–387 (2013)

    Article  CAS  Google Scholar 

  14. H. Namkung-Matthai, R. Appleyard, J. Jansen, J. Hao Lin, S. Maastricht, M. Swain, R.S. Mason, G.A. Murrell, A.D. Diwan, T. Diamond, Osteoporosis influences the early period of fracture healing in a rat osteoporotic model. Bone 28(1), 80–86 (2001)

    Article  CAS  Google Scholar 

  15. K. Jensen, R. Krusenstjerna-Hafstrom, J. Lohse, K.H. Petersen, H. Derand, A novel quantitative immunohistochemistry method for precise protein measurements directly in formalin-fixed, paraffin-embedded specimens: analytical performance measuring HER2. Mod. Pathol. 30(2), 180–193 (2017)

    Article  CAS  Google Scholar 

  16. T.D. Rachner, S. Khosla, L.C. Hofbauer, Osteoporosis: now and the future. Lancet 377(9773), 1276–1287 (2011)

    Article  CAS  Google Scholar 

  17. P.J. Marie, M. Kassem, Osteoblasts in osteoporosis: past, emerging, and future anabolic targets. Eur. J. Endocrinol. 165(1), 1–10 (2011)

    Article  CAS  Google Scholar 

  18. Y. Miyauchi, Y. Sato, T. Kobayashi, S. Yoshida, T. Mori, H. Kanagawa, E. Katsuyama, A. Fujie, W. Hao, K. Miyamoto, T. Tando, H. Morioka, M. Matsumoto, P. Chambon, R.S. Johnson, S. Kato, Y. Toyama, T. Miyamoto, HIF1alpha is required for osteoclast activation by estrogen deficiency in postmenopausal osteoporosis. Proc. Natl. Acad. Sci. USA 110(41), 16568–16573 (2013)

    Article  CAS  Google Scholar 

  19. L.M. Havill, L.G. Hale, D.E. Newman, S.M. Witte, M.C. Mahaney, Bone, ALP and OC reference standards in adult baboons (Papio hamadryas) by sex and age. J. Med. Primatol. 35(2), 97–105 (2006)

    Article  CAS  Google Scholar 

  20. C. Li, Z. Jiang, X. Liu, Biochemical mechanism of gallium on prevention of fatal cage-layer osteoporosis. Biol. Trace Elem. Res. 134(2), 195–202 (2010)

    Article  CAS  Google Scholar 

  21. S. Zenger, K. Hollberg, J. Ljusberg, M. Norgard, B. Ek-Rylander, R. Kiviranta, G. Andersson, Proteolytic processing and polarized secretion of tartrate-resistant acid phosphatase is altered in a subpopulation of metaphyseal osteoclasts in cathepsin K-deficient mice. Bone 41(5), 820–832 (2007)

    Article  CAS  Google Scholar 

  22. Z. Tang, P.E. Scherer, T. Okamoto, K. Song, C. Chu, D.S. Kohtz, I. Nishimoto, H.F. Lodish, M.P. Lisanti, Molecular cloning of caveolin-3, a novel member of the caveolin gene family expressed predominantly in muscle. J. Biol. Chem. 271(4), 2255–2261 (1996)

    Article  CAS  Google Scholar 

  23. Z. Wang, N. Wang, W. Li, P. Liu, Q. Chen, H. Situ, S. Zhong, L. Guo, Y. Lin, J. Shen, J. Chen, Caveolin-1 mediates chemoresistance in breast cancer stem cells via beta-catenin/ABCG2 signaling pathway. Carcinogenesis 35(10), 2346–2356 (2014)

    Article  CAS  Google Scholar 

  24. J. Korvala, H. Juppner, O. Makitie, E. Sochett, D. Schnabel, S. Mora, C.F. Bartels, M.L. Warman, D. Deraska, W.G. Cole, H. Hartikka, L. Ala-Kokko, M. Mannikko, Mutations in LRP5 cause primary osteoporosis without features of OI by reducing Wnt signaling activity. Bmc. Med. Genet. 13, 26 (2012)

    Article  CAS  Google Scholar 

  25. M. Rossini, D. Gatti, S. Adami, Involvement of WNT/beta-catenin signaling in the treatment of osteoporosis. Calcif. Tissue Int. 93(2), 121–132 (2013)

    Article  CAS  Google Scholar 

  26. R.K. Bikkavilli, C.C. Malbon, Arginine methylation of G3BP1 in response to Wnt3a regulates beta-catenin mRNA. J. Cell. Sci. 124(Pt 13), 2310–2320 (2011)

    Article  CAS  Google Scholar 

  27. J. Chen, F. Long, beta-catenin promotes bone formation and suppresses bone resorption in postnatal growing mice. J. Bone Miner. Res. 28(5), 1160–1169 (2013)

    Article  CAS  Google Scholar 

  28. J. Su, A. Zhang, Z. Shi, F. Ma, P. Pu, T. Wang, J. Zhang, C. Kang, Q. Zhang, MicroRNA-200a suppresses the Wnt/beta-catenin signaling pathway by interacting with beta-catenin. Int. J. Oncol. 40(4), 1162–1170 (2012)

    CAS  PubMed  Google Scholar 

  29. Z. von Marschall, L.W. Fisher, Secreted Frizzled-related protein-2 (sFRP2) augments canonical Wnt3a-induced signaling. Biochem. Biophys. Res. Commun. 400(3), 299–304 (2010)

    Article  Google Scholar 

  30. S. Iyer, E. Ambrogini, S.M. Bartell, L. Han, P.K. Roberson, R. de Cabo, R.L. Jilka, R.S. Weinstein, C.A. O’Brien, S.C. Manolagas, M. Almeida, FOXOs attenuate bone formation by suppressing Wnt signaling. J. Clin. Invest. 123(8), 3409–3419 (2013)

    Article  CAS  Google Scholar 

  31. J. Wang, J.S. Park, Y. Wei, M. Rajurkar, J.L. Cotton, Q. Fan, B.C. Lewis, H. Ji, J. Mao, TRIB2 acts downstream of Wnt/TCF in liver cancer cells to regulate YAP and C/EBPalpha function. Mol. Cell 51(2), 211–225 (2013)

    Article  CAS  Google Scholar 

  32. S. Bousserouel, M. Raymondjean, A. Brouillet, G. Bereziat, M. Andreani, Modulation of cyclin D1 and early growth response factor-1 gene expression in interleukin-1beta-treated rat smooth muscle cells by n-6 and n-3 polyunsaturated fatty acids. Eur. J. Biochem. 271(22), 4462–4473 (2004)

    Article  CAS  Google Scholar 

  33. F. Fang, W.Y. Zhao, R.K. Li, X.M. Yang, J. Li, J.P. Ao, S.H. Jiang, F.Z. Kong, L. Tu, C. Zhuang, W.X. Qin, P. He, W.M. Zhang, H. Cao, Z.G. Zhang, Silencing of WISP3 suppresses gastric cancer cell proliferation and metastasis and inhibits Wnt/beta-catenin signaling. Int. J. Clin. Exp. Pathol. 7(10), 6447–6461 (2014)

    PubMed  PubMed Central  Google Scholar 

  34. N. Pecina-Slaus, Wnt signal transduction pathway and apoptosis: a review. Cancer Cell. Int. 10, 22 (2010)

    Article  Google Scholar 

  35. H. Yamamoto, H. Komekado, A. Kikuchi, Caveolin is necessary for Wnt-3a-dependent internalization of LRP6 and accumulation of beta-catenin. Dev. Cell. 11(2), 213–223 (2006)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would like to acknowledge the helpful comments on this paper received from our reviewers.

Funding

This study was supported by Fuzhou Science and Technology Bureau (No. 2013-S-123-4) and Natural Science Foundation of Fujian Province (No. 2016J01598).

Author information

Author notes

  1. These authors are regarded as co-first authors: Run-Bao Yang, Feng-Fei Lin.

Authors and Affiliations

  1. Department of Orthopedics and Traumatology, Longyan First Hospital, Longyan, 364000, P. R. China

    Run-Bao Yang, Jun Yang, Ming-Hua Zhang, Qiao-Ping Lu, Bo Xiao & Yan Liu

  2. Department of Orthopedic Surgery, Fuzhou Second Hospital, Fuzhou, 350007, P. R. China

    Feng-Fei Lin, Bin Chen & Ke Zheng

  3. Department of Orthopaedics Surgery, Longyan First Hospital, Longyan, 364000, P. R. China

    Yong-Rong Qiu

Authors
  1. Run-Bao Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Feng-Fei Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jun Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bin Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ming-Hua Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Qiao-Ping Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bo Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ke Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yong-Rong Qiu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yong-Rong Qiu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All animal operations in this study were performed was in line with the local principles of management and use of experimental animals.

Additional information

This article has been retracted. Please see the retraction notice for more detail:https://doi.org/10.1007/s12020-022-03032-9

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, RB., Lin, FF., Yang, J. et al. RETRACTED ARTICLE: Overexpression of CAV3 facilitates bone formation via the Wnt signaling pathway in osteoporotic rats. Endocrine 63, 639–650 (2019). https://doi.org/10.1007/s12020-018-1803-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-018-1803-1

Keywords

Search

Navigation