Regulation of osteoclast structure and function by FAK family kinases

Journal of Leukocyte Biology

Keena Thomas¹  Cynthia S. Huang²  Edward A. Botchwey  and²  Michael F. Gutknecht¹  Amy H. Bouton¹  Brianne J. Ray¹ 

[1] Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia, USA; The Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Atlanta, Georgia, USA Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia, USA;

关键词: Pyk2;    podosome;    M-CSF;   

DOI  :  10.1189/jlb.0512259

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Osteoclasts are highly specialized cells that resorb bone and contribute to bone remodeling. Diseases such as osteoporosis and osteolytic bone metastasis occur when osteoclast-mediated bone resorption takes place in the absence of concurrent bone synthesis. Considerable effort has been placed on identifying molecules that regulate the bone resorption activity of osteoclasts. To this end, we investigated unique and overlapping functions of members of the FAK family (FAK and Pyk2) in osteoclast functions. With the use of a conditional knockout mouse model, in which FAK is selectively targeted for deletion in osteoclast precursors (FAKΔmyeloid), we found that loss of FAK resulted in reduced bone resorption by osteoclasts in vitro, coincident with impaired signaling through the CSF-1R. However, bone architecture appeared normal in FAKΔmyeloid mice, suggesting that Pyk2 might functionally compensate for reduced FAK levels in vivo. This was supported by data showing that podosome adhesion structures, which are essential for bone degradation, were significantly more impaired in osteoclasts when FAK and Pyk2 were reduced than when either molecule was depleted individually. We conclude that FAK contributes to cytokine signaling and bone resorption in osteoclasts and partially compensates for the absence of Pyk2 to maintain proper adhesion structures in these cells.

【 授权许可】

Unknown