Focal adhesion proteins in skeleton and diseases

FA signaling in cartilage. Integrins are transmembrane proteins connecting chemical and mechanical stimuli between the outside ECMs and inside of chondrocytes. The integrin-mediated signaling pathway is critical for osteoarthritis (OA) development. Peptides and fibronectin fragments containing the RGD cell binding sequence can bind to integrins and other the FA proteins which promotes expression of a number of pro-inflammatory mediators and matrix degrading enzymes. The combined effects of increased ligands as a result of cartilage damage may enable cells within OA joints to elicit pathogenic responses, and thereby drive the progression of OA. In response to integrin activation, PYK2 and/or FAK are recruited to a signaling complex that consists of Src, paxillin, vinculin, talin and kindlin, which result in activation of PI3K and/or MAPK that may lead to cell adhesion and migration. Further, development of OA may result from chronic signaling of inflammatory, catabolic, and hypertrophic molecules as well as other integrin effectors as a result of the increased levels of both ligand and receptor components following joint injury. Furthermore, kindlin-2 is related to mitochondrial oxidative stress and chondrocyte catabolism. In addition, kindlin-2 serves as a major controlling factor in the regulation of the chondrogenesis during prenatal and postnatal skeletal development by regulating TGF-β signalling and Sox 9 expression.

Publication

Roles of focal adhesion proteins in skeleton and diseases. (2023) Sheng Chen, et al. Acta Pharm Sin B. 2023 Mar;13(3):998-1013. Figure: F3. Homo sapiens

Disease mentions