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Limited roles of Piezo mechanosensing channels in articular cartilage development and osteoarthritis progression

  • C. Young
    Endocrine Unit, Massachusetts General Hospital, 50 Blossom Street, Boston, MA 02114, USA
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  • T. Kobayashi
    Address correspondence and reprint requests to: T. Kobayashi, Endocrine Unit, Massachusetts General Hospital, 50 Blossom Street, Boston, MA 02114, USA.
    Endocrine Unit, Massachusetts General Hospital, 50 Blossom Street, Boston, MA 02114, USA

    Harvard Medical School, Boston, MA, USA
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Published:February 17, 2023DOI:



      To investigate the role of Piezo1 and Piezo2 in surgically induced osteoarthritis (OA) in mice.


      Male conditional knockout (cKO) mice missing Piezo1 and Piezo2 in the joint using Gdf5-Cre transgenic mice were induced with post-traumatic OA by destabilization of the medial meniscus (DMM) of the right knee joint at 12 weeks of age. The severity of OA was histologically assessed at 24 weeks of age. OA-associated pain was evaluated by static weight bearing analysis. Additionally, articular chondrocytes isolated from cKO mice were exposed to fluid flow shear stress (FFSS) to evaluate the expression of OA-associated genes.


      Mice with conditional deletion of Piezo1 and Piezo2 showed normal joint development with no overt histological changes in the knee joint at 12 weeks and 24 weeks. DMM surgery induced moderate to severe OA in both control and cKO mice (median OARSI score: control, 4.67; cKO, 4.23, P = 0.3082), although a few cKO mice showed milder OA. Pain assessment by static weight-bearing analysis suggested Piezo ablation in the joint has no beneficial effects on pain. FFSS increased the expression of OA-related genes both in control and cKO mice to similar extents.


      Piezo1 and Piezo2 are not essential for normal joint development. Genetic ablation of Piezo channels did not confer evident protective effects on OA progression in mice. In vitro data suggests that different mechanotransducers other than Piezo channels mediate FFSS in mechanical stress-induced gene expression.


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        • Zhao Z.
        • Li Y.
        • Wang M.
        • Zhao S.
        • Zhao Z.
        • Fang J.
        Mechanotransduction pathways in the regulation of cartilage chondrocyte homoeostasis.
        J Cell Mol Med. 2020; 24: 5408-5419
        • Gao W.
        • Hasan H.
        • Anderson D.E.
        • Lee W.
        The role of mechanically-activated ion channels Piezo1, Piezo2, and TRPV4 in chondrocyte mechanotransduction and mechano-therapeutics for osteoarthritis.
        Front Cell Dev Biol. 2022; 10885224
        • McNulty A.L.
        • Leddy H.A.
        • Liedtke W.
        • Guilak F.
        TRPV4 as a therapeutic target for joint diseases.
        Naunyn Schmiedebergs Arch Pharmacol. 2015; 388: 437-450
        • O'Conor C.J.
        • Ramalingam S.
        • Zelenski N.A.
        • Benefield H.C.
        • Rigo I.
        • Little D.
        • et al.
        Cartilage-specific knockout of the mechanosensory ion channel TRPV4 decreases age-related osteoarthritis.
        Sci Rep. 2016; 629053
        • Qin L.
        • He T.
        • Chen S.
        • Yang D.
        • Yi W.
        • Cao H.
        • et al.
        Roles of mechanosensitive channel Piezo1/2 proteins in skeleton and other tissues.
        Bone Res. 2021; 9: 44
        • Lee W.
        • Leddy H.A.
        • Chen Y.
        • Lee S.H.
        • Zelenski N.A.
        • McNulty A.L.
        • et al.
        Synergy between Piezo1 and Piezo2 channels confers high-strain mechanosensitivity to articular cartilage.
        Proc Natl Acad Sci U S A. 2014; 111: E5114-E5122
        • Mehana E.E.
        • Khafaga A.F.
        • El-Blehi S.S.
        The role of matrix metalloproteinases in osteoarthritis pathogenesis: an updated review.
        Life Sci. 2019; 234116786
        • Molnar V.
        • Matisic V.
        • Kodvanj I.
        • Bjelica R.
        • Jelec Z.
        • Hudetz D.
        • et al.
        Cytokines and chemokines involved in osteoarthritis pathogenesis.
        Int J Mol Sci. 2021; : 22
        • Lee W.
        • Nims R.J.
        • Savadipour A.
        • Zhang Q.
        • Leddy H.A.
        • Liu F.
        • et al.
        Inflammatory signaling sensitizes Piezo1 mechanotransduction in articular chondrocytes as a pathogenic feed-forward mechanism in osteoarthritis.
        Proc Natl Acad Sci U S A. 2021; : 118
        • Rountree R.B.
        • Schoor M.
        • Chen H.
        • Marks M.E.
        • Harley V.
        • Mishina Y.
        • et al.
        BMP receptor signaling is required for postnatal maintenance of articular cartilage.
        PLoS Biol. 2004; 2: e355
        • Glasson S.S.
        • Blanchet T.J.
        • Morris E.A.
        The surgical destabilization of the medial meniscus (DMM) model of osteoarthritis in the 129/SvEv mouse.
        Osteoarthritis Cartilage. 2007; 15: 1061-1069
        • Glasson S.S.
        • Chambers M.G.
        • Van Den Berg W.B.
        • Little C.B.
        The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the mouse.
        Osteoarthritis Cartilage. 2010; 18: S17-S23
        • Ogawa H.
        • Kozhemyakina E.
        • Hung H.H.
        • Grodzinsky A.J.
        • Lassar A.B.
        Mechanical motion promotes expression of Prg4 in articular cartilage via multiple CREB-dependent, fluid flow shear stress-induced signaling pathways.
        Genes Dev. 2014; 28: 127-139
        • Nie X.
        • Chung M.K.
        Piezo channels for skeletal development and homeostasis: insights from mouse genetic models.
        Differentiation. 2022; 126: 10-15
        • Jones R.C.
        • Lawrence K.M.
        • Higgins S.M.
        • Richardson S.M.
        • Townsend P.A.
        Urocortin-1 is chondroprotective in response to acute cartilage injury via modulation of Piezo1.
        Int J Mol Sci. 2022; 23