Type H Vessels Are Progressively Lost in a Mouse Model of Periodontitis: A 3D Tissue-clearing Analysis of Alveolar Bone.

Purpose: Type H vessels, a specialized subtype of bone-forming vasculature first identified in long bones, are now recognized as critical regulators of angiogenesis-osteogenesis coupling. Defined by high expression of CD31 and endomucin (EMCN), these vessels contribute to both physiological bone growth and pathological bone loss. Although recent studies have identified type H vessels in alveolar bone, their three-dimensional (3D) organization and responses to inflammation remain poorly understood. Here, we aimed to establish a reproducible methodology for visualizing and quantifying type H vessels in murine alveolar bones under both healthy and inflammatory conditions, utilizing a mouse model of periodontitis. Methods: , and changes in EMCN and CD31 expression were analyzed by qPCR and flow cytometry. Results: suppressed the expression of EMCN, a hallmark molecule of type H vessels, in BMECs. Conclusion: This study provides the first 3D visualization and quantitative characterization of type H vessels in murine alveolar bone with or without periodontitis using a tissue-clearing-based approach. We demonstrate that inflammatory conditions associated with periodontitis cause marked loss of type H vasculature, thereby disrupting angiogenesis-osteogenesis coupling. These findings underscore the possible role of the vascular niche in periodontal disease pathogenesis and suggest that therapeutic preservation or restoration of type H vessels could represent a novel strategy to prevent inflammation-driven alveolar bone loss and enhance periodontal regeneration.