Redox-active endosomes mediate α5β1 integrin signaling and promote chondrocyte matrix metalloproteinase production in osteoarthritis.

ABSTRACT: Mechanical cues sensed by integrins induce cells to produce proteases to remodel the extracellular matrix. Excessive protease production occurs in many degenerative diseases, including osteoarthritis, in which articular cartilage degradation is associated with the genesis of matrix protein fragments that can activate integrins. We investigated the mechanisms by which integrin signals may promote protease production in response to matrix changes in osteoarthritis. Using a fragment of the matrix protein fibronectin (FN) to activate the α5β1 integrin in primary human chondrocytes, we found that endocytosis of the integrin and FN fragment complex drove the production of the matrix metalloproteinase MMP-13. Activation of α5β1 by the FN fragment, but not by intact FN, was accompanied by reactive

SUBMITTER: Miao MZ 

PROVIDER: S-EPMC10666734 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature