The effects of kindlin3 on osteoclast function

TL;DRAbstract

Osteoclasts are a bone cell type responsible for the breakdown of bone. They display cell surface integrins that help activate signaling cascades that control the differentiation and function of osteoclasts. The kindlins are a family of proteins that are involved in activating integrin function and enhancing cell attachment to substrates. Kindlin3 is expressed solely in hematopoietic cells, including osteoclasts and their precursors. Mutations in kindlin3 are associated with a human syndrome, Leukocyte Adhesion Deficiency III (LAD-III) whose symptoms include osteopetrosis, which is bone brittleness due to non-functioning osteoclasts. The kindlin3 C-terminal tail is composed of three FERM (integrin-binding) domains, F1, F2, and F3 and one PH (membrane lipid-binding) domain that interrupts the F2 domain. The goal of this work is to determine the roles of kindlin3 and its domains in affecting osteoclast differentiation and function. Our studies demonstrated that kindlin3 is upregulated du

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