Filamin A protects cells against force‐induced apoptosis by stabilizing talin‐ and vinculin‐containing cell adhesions

In mechanically loaded tissues such as weight‐bearing joints, myocardium, and periodontal ligament, pathophysiological forces can disrupt cell‐matrix contacts, which can induce cell death, leading to tissue and organ dysfunction. Protection against force‐induced cell death may be mediated by filamin A (FLNa), an actin‐binding protein that regulates β1 integrin‐mediated cell adhesion. We examined the affect of filamin expression on collagen distribution and cell death in the periodontal ligament, a force‐loaded tissue. Conditional deletion of FLNa in fibroblasts was associated with 2‐fold increase of acellular areas in periodontal ligament and 7‐fold higher proportions of apoptotic cells. In cultured fibroblasts with FLNa knockdown, we examined the affect of supraphysiological forces (1 pN/μm2 cell area; applied through the β1 integrin) on recruitment of talin and vinculin to focal adhesions and on apoptosis. Compared with the wild type, FLNa‐knockdown cells exhibited 3‐fold increases in floating cells after overnight force application and a 2‐fold increase in cell detachment. Force induced time‐dependent reductions (P