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Mediation of Rac1 activation by kindlin‐2: An essential function in osteoblast adhesion, spreading, and proliferation
Author(s) -
Jung GilYong,
Park YoonJeong,
Han JungSuk
Publication year - 2011
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.23178
Subject(s) - microbiology and biotechnology , osteoblast , rac1 , integrin , cell adhesion , gene knockdown , focal adhesion , adhesion , chemistry , cell growth , signal transduction , biology , cell , biochemistry , apoptosis , organic chemistry , in vitro
Kindlins are focal adhesion proteins that regulate integrin signaling. Although integrin activation is critical for bone development, little is known about the expression and role of kindlins in osteoblasts. We therefore investigated the function of kindlin‐2 in osteoblast adhesion, spreading, and proliferation using small interfering RNA. In MC3T3‐E1 cells, only kindlin‐2 is highly expressed and localizes to focal adhesion. We found that kindlin‐2 was involved in integrin activation in MC3T3‐E1 cells and that kindlin‐2 knockdown osteoblasts resulted in diminished cell adhesion, spreading, and proliferation. In this process, kindlin‐2 knockdown impaired transient Rac1 activation, influencing Akt activation and AP‐1 activity. In agreement with these data, pharmacological inhibition of Rac1 reduced MC3T3‐E1 cell adhesion, spreading, and proliferation. Overall, these findings demonstrated that kindlin‐2 governs Rac1 activation, which controls osteoblast function. Our findings provide the first insights concerning the function of kindlin‐2 in osteoblast, and suggest that kindlin‐2 is a critical mediator for osteoblast physiology. J. Cell. Biochem. 112: 2541–2548, 2011. © 2011 Wiley‐Liss, Inc.