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Targeting calcium-related mechanotransduction in early OA

Nature Reviews Rheumatology volume 17, pages 445–446 (2021)Cite this article

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Sensation of mechanical stimuli by chondrocytes is critical to cartilage homeostasis and osteoarthritis development. The earliest responses in chondrocyte mechanotransduction pathways involve calcium influx and changes in mitochondrial function, which occur in seconds to minutes. Deeper understanding of these events can elucidate new therapeutic targets for early intervention to prevent osteoarthritis.

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Fig. 1: Chondrocyte mechanotransduction pathways in posttraumatic osteoarthritis pathogenesis.

References

  1. Lee, W. et al. Inflammatory signaling sensitizes Piezo1 mechanotransduction in articular chondrocytes as a pathogenic feed-forward mechanism in osteoarthritis. Proc. Natl Acad. Sci. USA 118, e2001611118 (2021).

    Article  CAS  Google Scholar 

  2. Agarwal, P. et al. A dysfunctional TRPV4–GSK3β pathway prevents osteoarthritic chondrocytes from sensing changes in extracellular matrix viscoelasticity. Nat. Biomed. Eng. https://doi.org/10.1038/s41551-021-00691-3 (2021).

    Article  PubMed  Google Scholar 

  3. Grodzinsky, A. J. et al. Cartilage tissue remodeling in response to mechanical forces. Annu. Rev. Biomed. Eng. 2, 691–713 (2000).

    Article  CAS  Google Scholar 

  4. Bartell, L. R. et al. Mitoprotective therapy prevents rapid, strain-dependent mitochondrial dysfunction after articular cartilage injury. J. Orthop. Res. 38, 1257–1267 (2020).

    Article  CAS  Google Scholar 

  5. Delco, M. L. et al. Mitochondrial dysfunction is an acute response of articular chondrocytes to mechanical injury. J. Orthop. Res. 36, 739–750 (2018).

    Article  CAS  Google Scholar 

  6. Zhang, K. et al. Mechanosensory and mechanotransductive processes mediated by ion channels in articular chondrocytes: Potential therapeutic targets for osteoarthritis. Channels 15, 339–359 (2021).

    Article  Google Scholar 

  7. Lee, W. et al. Synergy between Piezo1 and Piezo2 channels confers high-strain mechanosensitivity to articular cartilage. Proc Natl Acad. Sci. USA 111, E5114–22 (2014).

    Article  CAS  Google Scholar 

  8. Genes, N. G. et al. Effect of substrate mechanics on chondrocyte adhesion to modified alginate surfaces. Arch. Biochem. Biophys. 422, 161–167 (2004).

    Article  CAS  Google Scholar 

  9. Oo, W. M. et al. Disease-modifying drugs in osteoarthritis: current understanding and future therapeutics. Expert Opin. Emerg. Drugs 23, 331–347 (2018).

    Article  CAS  Google Scholar 

  10. Bartell, L. R. et al. Measuring microscale strain fields in articular cartilage during rapid impact reveals thresholds for chondrocyte death and a protective role for the superficial layer. J. Biomech. 18, 3440–3446 (2015).

    Article  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Lisa Fortier and Itai Cohen for their helpful discussions on this topic. Funding was provided by NSF CMMI 1927197 (L.J.B.), NIH 1R03AR075929-01 (M.L.D.), NIH 5K08AR068470-02 (M.L.D.) and NIH 1R01AR071394-01 (L.J.B.).

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Authors and Affiliations

  1. Department of Clinical Science, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA

    Michelle L. Delco

  2. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA

    Lawrence J. Bonassar

  3. Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, USA

    Lawrence J. Bonassar

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  1. Michelle L. Delco
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  2. Lawrence J. Bonassar
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Correspondence to Lawrence J. Bonassar.

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Competing interests

L.J.B. is a co-founder and holds equity in 3DBio Therapeutics, which develops engineered cartilage for therapeutic applications. M.L.D has no competing interests.

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Delco, M.L., Bonassar, L.J. Targeting calcium-related mechanotransduction in early OA. Nat Rev Rheumatol 17, 445–446 (2021). https://doi.org/10.1038/s41584-021-00649-4

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