Cathepsin K inhibition alleviates periodontal bone resorption by promoting type H vessel formation through PDGF-BB/PDGFR-β axis.

Abstract

To explore the effects of cathepsin K (CTSK) inhibition on type H vessel formation and alveolar bone resorption within periodontitis. Conditioned media derived from preosteoclasts pretreated with the CTSK inhibitor odanacatib (ODN), ODN supplemented small interfering RNA targeting PDGF-BB (si-PDGF-BB), or PBS were prepared, to assess their proangiogenic effects on endothelial cells (HUVECs). A series of angiogenic-related assays were conducted to evaluate HUVEC proliferation, migration, and tube formation abilities invitro. In addition, qRT-PCR and Western blot assays were employed to examine the expression levels of genes/proteins related to PDGF-BB/PDGFR-β axis components. A mouse periodontitis model was established to evaluate the effects of CTSK inhibition on type H vessel formation. CTSK inhibition promoted PDGF-BB secretion from preosteoclasts and proliferation, migration, and tube formation activities of HUVECs invitro. However, the conditioned medium from preosteoclasts pretreated by si-PDGF-BB impaired the angiogenic activities of HUVECs. This promoted angiogenesis function by CTSK inhibition may be mediated by the PDGF-BB/PDGFR-β axis. Functionally, invivo studies demonstrated that CTSK inhibition significantly accelerated type H vessel formation and alleviated bone loss within periodontitis. CTSK inhibition promotes type H vessel formation and attenuates alveolar bone resorption within periodontitis via PDGF-BB/PDGFR-β axis.