%0 Journal Article
%T The stiffness and collagen control differentiation of osteoclasts with an altered expression of c-Src in podosome.
%A Urano K
%A Tanaka Y
%A Tominari T
%A Takatoya M
%A Arai D
%A Miyata S
%A Matsumoto C
%A Miyaura C
%A Numabe Y
%A Itoh Y
%A Hirata M
%A Inada M
%J Biochem Biophys Res Commun
%V 704
%N 0
%D 2024 Apr 16
%M 38402724
%F 3.322
%R 10.1016/j.bbrc.2024.149636
%X Osteoclasts are hematopoietic cells attached to the bones containing type I collagen-deposited hydroxyapatite during bone resorption. Two major elements determine the stiffness of bones: regular calcified bone (bone that is resorbable by osteoclasts) and un-calcified osteoid bone (bone that is un-resorbable by osteoclasts). The osteolytic cytokine RANKL promotes osteoclast differentiation; however, the roles of the physical interactions of osteoclasts with calcified and un-calcified bone at the sealing zones and the subsequent cellular signaling remain unclear. In this study, we investigated podosomes, actin-rich adhesion structures (actin-ring) in the sealing zone that participates in sensing hard stiffness with collagen in the physical environment during osteoclast differentiation. RANKL-induced osteoclast differentiation induction was promoted when Raw264.7 cells were cultured on collagen-coated plastic dishes but not on non-coated plastic dishes, which was associated with the increased expression of podosome-related genes and Src. In contrast, when cells were cultured on collagen gel, expression of podosome-related genes and Src were not upregulated. The induction of podosome-related genes and Src requires hard stiffness with RGD-containing substratum and integrin-mediated F-actin polymerization. These results indicate that osteoclasts sense both the RGD sequence and stiffness of calcified collagen through their podosome components regulating osteoclast differentiation via the c-Src pathway.