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

Abstract

AbstractObjectivesTo explore the effects of cathepsin K (CTSK) inhibition on type H vessel formation and alveolar bone resorption within periodontitis.MethodsConditioned 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 in vitro. 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.ResultsCTSK inhibition promoted PDGF‐BB secretion from preosteoclasts and proliferation, migration, and tube formation activities of HUVECs in vitro. 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, in vivo studies demonstrated that CTSK inhibition significantly accelerated type H vessel formation and alleviated bone loss within periodontitis.ConclusionCTSK inhibition promotes type H vessel formation and attenuates alveolar bone resorption within periodontitis via PDGF‐BB/PDGFR‐β axis.