Excessive osteoclast leads to the imbalance in bone reconstruction and results in osteolytic diseases, such as osteoporosis and rheumatic arthritis. Integrin α_vβ₃ abundantly expresses on osteoclast and plays a critical role in the formation and function of osteoclast, therefore, blockage of α_vβ₃ has become an attractive therapeutic option for osteolytic diseases. In this study, we find that Tablysin-15, a RGD motif containing disintegrin, concentration-dependently suppresses RANKL-induced osteoclastogenesis, F-actin ring formation and bone resorption without affecting the cell viabilities. Tablysin-15 binds to integrin α_vβ₃ and inhibits the activation of FAK-associated signaling pathways. Tablysin-15 also suppresses the activation of NF-кB, MAPK, and Akt-NFATc1 signaling pathways, which are crucial transcription factors during osteoclast differentiation. Moreover, Tablysin-15 decreases the osteoclastogenesis marker gene expression, including MMP-9, TRAP, CTSK, and c-Src. Finally, Tablysin-15 significantly inhibits LPS‐induced bone loss in a mouse model. Taken together, our results indicate that Tablysin-15 significantly suppresses osteoclastogenesis in vitro and in vivo, thus it might be a excellent candidate for treating osteolytic‐related diseases.

破骨细胞过多会导致骨骼重建失衡，并导致溶骨性疾病，例如骨质疏松症和风湿性关节炎。整合素α _v β ₃丰富地表达于破骨细胞和起着破骨细胞的形成和功能中起关键作用，因此，α的堵塞_v β ₃成为溶骨性疾病的有吸引力的治疗选择。在这项研究中，我们发现TABLESIN-15（一种包含解整合素的RGD图案）浓度依赖性地抑制RANKL诱导的破骨细胞生成，F-肌动蛋白环形成和骨吸收，而不会影响细胞活力。Tablysin-15结合于整合素α _v β ₃并抑制FAK相关信号通路的激活。TABLESIN-15还抑制破骨细胞分化过程中至关重要的转录因子NF-кB，MAPK和Akt-NFATc1信号通路的激活。此外，TABLESIN-15会降低破骨细胞生成标记基因的表达，包括MMP-9，TRAP，CTSK和c-Src。最后，TABLESIN-15在小鼠模型中显着抑制LPS诱导的骨质流失。总之，我们的结果表明，Tablysin-15显著抑制破骨细胞在体外和体内，因此它可能是用于治疗溶骨性相关疾病的优秀候选人。