Piezo1 deficiency in monocytes accelerates periodontal bone loss via increased local migration and osteoclastogenesis 9213

Abstract Description Objectives Piezo1, a mechanosensitive Ca²? channel, plays a critical role in regulating various immune cell functions. However, the role of Piezo1 expressed on monocytes (MCs) infiltrating in infectious inflammatory bone lytic lesions remains unclear. We examined the effect of Piezo1 expressed by MC-derived pre-osteoclasts (preOCs) on their migration and local OC differentiation in a mouse periodontitis model. Methods Periodontitis was induced by ligature attachment to the molars of LysMcre/Piezo1flox/flox (Piezo1ΔLysM) or Piezo1flox/flox (control) mice for 7 days. Bone loss was assessed by micro-CT-bone morphometry. The infiltration of CD11b? preOCs to alveolar bone was analyzed by flow cytometry. PreOCs from Piezo1ΔLysM or control mice were introduced to endothelial cells (ECs) cultured in a microfluidics system (ibidi inc) under shear stress (5 or 20 dyn/cm²) and trans-EC migrations were monitored by fluorescence microscopy. Results Piezo1ΔLysM mice showed significantly greater CD11b+ cell infiltration and bone loss in the periodontitis lesion than control mice (P < 0.01). The control pre-OCs trans-EC migrated more in 5 dyn/cm² than 20 dyn/cm. Such an elevated trans-EC-migration at 5 dyn/cm² was annulled by Piezo1ΔlysM-preOCs. Conclusion Stimulation of Piezo1 expressed on preOCs seemed to downregulate their trans-EC-migration and local OC-genesis in periodontitis, highlighting Piezo1 as a potential therapeutic target for infectious inflammatory bone lytic diseases. Funding Sources This study was supported by NIH grants: DE-027851, DE-028715, DE-331851, DE-032907, GM-150469, DE025255 and DE032156 Topic Categories Cellular Adhesion, Migration, and Inflammation (CAM)