Objectives: To explore the effects of cathepsin K (CTSK) inhibition on type H vessel formation and alveolar bone resorption within periodontitis.
Methods: 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 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.
Results: CTSK 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.
Conclusion: CTSK inhibition promotes type H vessel formation and attenuates alveolar bone resorption within periodontitis via PDGF-BB/PDGFR-β axis.
Keywords: PDGF-BB; bone resorption; cathepsin K; periodontitis; type H vessel.
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