メカノバイオロジーからみた変形性関節症

Cartilage/chondrocyte research and osteoarthritis. Mechanobiology for development of osteoarthritis.

　運動刺激は軟骨細胞活動性・関節軟骨代謝を制御する最も重要な細胞外因子の一つで，過剰な非生理的運動刺激は病的メカノトランスダクションを介して変形性関節症を引き起こす。一方，適度な運動は疼痛軽減や関節機能回復，軟骨マトリックス分解酵素の発現低下などの有益な結果をもたらす。カルシウムシグナルはメカノトランスダクションの最初のステップで，近年の研究では，生理的運動刺激と過剰な非生理的運動刺激は異なる二つのカルシウムイオンチャネル（TRPV4とPiezo ion channels）を介していることが報告されている。本稿では，軟骨代謝・メカノトランスダクションに重要なカルシウムイオンチャネルについて概説する。

　Articular cartilage is exquisitely sensitive to their mechanical environment, and mechanical loading may be the most important external factor regulating cartilage metabolism. Mechanical loading regulates chondrocyte activity, and pathological excessive loading leads to abnormal mechanotransduction, which in turn induces cartilage degradation. Several studies report that moderate levels of exercise exerts beneficial effects, such as improvements in pain and physical function, and also mitigates joint destruction through the down-regulation of the expression of matrix proteases. Calcium signaling is an initial step in chondrocyte mechanotransduction that has been linked to many cellular processes, and recent studies found that calcium ion channels distinctively mechanically activated by physiological or pathological mechanical loading through transient receptor potential vanilloid 4（TRPV4）or Piezo ion channels. We review here the recent progress on mechanotransduction of chondocytes, highlighting the calcium ion channels.