Osteoprotegerin induces podosome disassembly in osteoclasts through calcium, ERK, and p38 MAPK signaling pathways.

摘要: Osteoclasts are critical for bone resorption and use podosomes to attach matrix. Osteoprotegerin (OPG) is a negative regulator of osteoclast function that can affect the formation podosomes. However, signaling pathways link OPG podosome have not been well characterized. Therefore, this study examined roles intracellular calcium MAPKs in OPG-induced disassembly osteoclasts. We assessed effects chelator Bapta-AM, ERK inhibitor U0126, p38 SB202190 on OPG-treated differentiation, adhesion structures, free Ca(2+) concentration phosphorylation state associated proteins (Pyk2 Src). Mouse monocytic RAW 264.7 cells were differentiated osteoclasts using RANKL (30ng/mL) M-CSF (25ng/mL). The pretreated with Bapta-AM (5μM), U0126 or (10μM) 30min, followed by 40ng/mL 3h. Osteoclastogenesis, structure, viability morphology, Pyk2 Src measured TRAP staining, scanning electron microscopy, real-time cell analyzer, flow cytometry western blotting, respectively. significantly inhibited osteoclastogenesis, reduced amount phosphorylated Src-pY527, but increased Src-pY416. partially restored differentiation structures. Both SB202190, levels concentration, Src-pY527. All three inhibitors blocked at These results suggest disrupts attachment structures activates as an adaptor protein competes through calcium- ERK-dependent pathways. MAPK may different role retraction. Our findings potentially offer novel insights into mechanisms downstream extracellular