Cathepsin K⁺ Non-Osteoclast Cells in the Skeletal System: Function, Models, Identity, and Therapeutic Implications

Cathepsin K (Ctsk) is a cysteine protease of the papain superfamily initially identified in differentiated osteoclasts; it plays a critical role in degrading the bone matrix. However, subsequent in vivo and in vitro studies based on animal models elucidate novel subpopulations of Ctsk-expressing cells, which display markers and properties of mesenchymal stem/progenitor cells. This review introduces the function, identity, and role of Ctsk⁺ cells and their therapeutic implications in related preclinical osseous disorder models. It also summarizes the available in vivo models for studying Ctsk⁺ cells and their progeny. Further investigations of detailed properties and mechanisms of Ctsk⁺ cells in transgenic models are required to guide potential therapeutic targets in multiple diseases in the future.