Occlusal Force Maintains Alveolar Bone Homeostasis via Type H Angiogenesis

作者：Ye Chen, Yijia Yin, Min Luo, Jiacheng Wu, Andrew Chen, Lei Deng, Liang Xie, Xianglong Han · 发表于：Journal of Dental Research · 年份：2023 · DOI：10.1177/00220345231191745 · 被引用次数：42 · 研究领域：Fibroblast Growth Factor Research、Hippo pathway signaling and YAP/TAZ、Erythrocyte Function and Pathophysiology

Physiologically, teeth and periodontal tissues are exposed to occlusal forces throughout their lifetime. Following occlusal unloading, unbalanced bone remodeling manifests as a net alveolar bone (AB) loss. This phenomenon is termed alveolar bone disuse osteoporosis (ABDO), the underlying mechanism of which remains unclear. Type H vessels, a novel capillary subtype tightly coupled with osteogenesis, reportedly have a role in skeletal remodeling; however, their role in ABDO is not well studied. In the present study, we aimed to explore the pathogenesis of and therapies for ABDO. The study revealed that type H endothelium highly positive for CD31 and endomucin was identified in the periodontal ligament (PDL) but rarely in the AB of the mice. In hypofunctional PDL, the density of type H vasculature and coupled osterix + (OSX + ) osteoprogenitors declined significantly. In addition, the angiogenic factor Slit guidance ligand 3 (SLIT3) was downregulated in the disused PDL, and periodontal injection of the recombinant SLIT3 protein partially ameliorated type H vessel dysfunction and AB loss in ABDO mice. With regard to the molecular mechanism, a mechanosensory signaling circuit, PIEZO1/Ca 2+ /HIF-1α/SLIT3, was validated by applying cyclic compression to 3-dimensional–cultured PDL cells using the Flexcell FX-5000 compression system. In summary, PDL plays a pivotal role in mechanotransduction by translating physical forces into the intracellular signaling axis PIEZO1/Ca 2+ /HIF-1α/SLI...