期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 92, 期 5, 页码 1021-1028出版社
OXFORD UNIV PRESS
DOI: 10.1189/jlb.0512259
关键词
Pyk2; podosome; M-CSF
资金
- U.S. National Institutes of Health [R21 CA135532, R01 DE019935, R01 AR056445]
- Department of Defense [BC073291, BC093524, W81XWH1010928]
- Charlottesville Women's 4-Miler Breast Cancer Research Fund
- National Cancer Institute Cancer Center [P30 CA44579]
- University of Virginia Cancer Center
- U.S. Department of Defense (DOD) [W81XWH1010928] Funding Source: U.S. Department of Defense (DOD)
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 (FAK(Delta myeloid)), 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 FAK(Delta myeloid) 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. J. Leukoc. Biol. 92: 1021-1028; 2012.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据