Cathepsin K inhibitors promote osteoclast-osteoblast communication and engagement of osteogenesis.

ABSTRACT: Cathepsin K inhibitors are well known for their inhibitory activity against bone resorption but were also reported to preserve bone formation in clinical trials, in contrast with other bone resorption antagonists. Here, we show cathepsin K inhibitors favor the crosstalk between osteoclasts and osteoblasts and help engaging the osteogenic process required for proper bone remodeling. Therefore, we used a novel approach, co-culturing human osteoclasts and osteoblast lineage cells on bone slices and monitoring through time-lapse their response to an active site (odanacatib) or an ectosteric (T06) cathepsin K inhibitor. Both inhibitors prevent the shift from pit to trench resorption mode and thus lead to a marked increase in pit-eroded surface lined with undigested collagen. Importantly, pit-er

SUBMITTER: Panwar P 

PROVIDER: S-EPMC12266958 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature