Real-time analysis of osteoclast resorption and fusion dynamics in response to bone resorption inhibitors.

ABSTRACT: Cathepsin K (CatK), an essential collagenase in osteoclasts (OCs), is a potential therapeutic target for the treatment of osteoporosis. Using live-cell imaging, we monitored the bone resorptive behaviour of OCs during dose-dependent inhibition of CatK by an ectosteric (Tanshinone IIA sulfonate) and an active site inhibitor (odanacatib). CatK inhibition caused drastic reductions in the overall resorption speed of OCs. At IC₅₀ CatK-inhibitor concentration, OCs reduced about 40% of their trench-forming capacity and at fourfold IC₅₀ concentrations, a > 95% reduction was observed. The majority of CatK-inhibited OCs (~ 75%) were involved in resorption-migration-resorption episodes forming adjacent pits, while ~ 25% were stagnating OCs which remained associated with the same

SUBMITTER: Panwar P 

PROVIDER: S-EPMC10978898 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature