Occlusal Force Maintains Alveolar Bone Homeostasis Via Type H Angiogenesis

To investigate the role of type H vessels and the mechanosensory signaling pathway in alveolar bone disuse osteoporosis (ABDO). Type H vessel density and osteoprogenitor (OSX+) levels were analyzed in hypofunctional periodontal ligament (PDL) and alveolar bone (AB) of mice. Recombinant SLIT3 was injected to assess its therapeutic effects. A mechanosensory pathway (PIEZO1/Ca²⁺/HIF-1α/SLIT3) was validated using cyclic compression on 3D-cultured PDL cells via the Flexcell FX-5000 system. Type H vessels (CD31⁺/endomucin⁺) were abundant in PDL but scarce in AB. Hypofunctional PDL showed reduced type H vasculature and OSX⁺ osteoprogenitors. SLIT3 downregulation in disused PDL correlated with AB loss, while SLIT3 injection partially restored type H vessel function and mitigated bone loss. The PIEZO1/Ca²⁺/HIF-1α/SLIT3 axis was confirmed as critical in mechanotransduction. PDL mediates mechanotransduction via PIEZO1/Ca²⁺/HIF-1α/SLIT3 to promote type H angiogenesis and osteogenesis, maintaining AB homeostasis. Targeting SLIT3 may offer novel therapeutic strategies for ABDO.