Osteoprotegerin disrupts peripheral adhesive structures of osteoclasts by modulating Pyk2 and Src activities
Osteoprotegerin has previously been shown to modulate bone mass by blocking osteoclast maturation and function.The detailed mechanisms of osteoprotegerin-induced disassembly of podosomes, disruption of adhesive structures and modulation of adhesion-related proteins in osteoclasts, however, are not well characterized.In this study, tartrate-resistant acidic phosphatase staining demonstrated that osteoprotegerin inhibited differentiation of osteoclasts.The use of scanning electron microscopy, real-time cell monitoring and confocal microscopy indicated that osteoclasts responded in a time and dose-dependent manner to osteoprotegerin treatments with retraction of peripheral adhesive structures and detachment from the extracellular substrate.Combined imaging and Western blot studies showed that osteoprotegerin induced dephosphorylation of Tyr 402 in Pyk2 and decreased its labeling in peripheral adhesion regions.Osteoprotegerin induced increased intracellular labeling of Tyr 402 in Pyk2, Tyr 416 in Src, increased dephosphorylation of Tyr 527 in Src, and increased Pyk2/Src association in the central region of osteoclasts.This evidence suggests that Src may function as an adaptor protein that competes for Pyk2 and relocates it from the peripheral adhesive zone to the central region of osteoclasts in response to osteoprotegerin treatment.Osteoprotegerin may induce podosome reassembly and peripheral adhesive structure detachment by modulating phosphorylation of Pyk2 and Src and their intracellular distribution in osteoclasts.
osteoprotegerin osteoclast podosome Src Pyk2
ZHAO Hongyan YUAN Yan BIAN Jianchun LIU Zongping LIU Xuezhong ZOU Hui DAI Nannan YAO Lulian ZHANG Xiao GAO Qian LIU Wei GU Jianhong
College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, P.R.China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, P.R.China
国内会议
中国畜牧兽医学会兽医内科与临床诊疗学分会第八届代表大会暨学术研讨会
大庆
英文
71-81
2015-07-22（万方平台首次上网日期，不代表论文的发表时间）