Matrix cross-linking-mediated mechanotransduction promotes posttraumatic osteoarthritis
Abstract
Osteoarthritic cartilage destruction is caused primarily by an imbalance between chondrocyte catabolism and anabolism. Various proinflammatory cytokines that disrupt this metabolic balance during osteoarthritis (OA) pathogenesis have been identified. Here, in addition to these biochemical pathways, we demonstrate that changes in the biophysical properties of the chondrocyte microenvironment triggered by cartilage matrix cross-linking play a causal role in OA pathogenesis. Two major OA risk factors, aging and mechanical stress, cause matrix stiffening via nonenzymatic and enzymatic collagen cross-linking through the accumulation of advanced glycation end-products and the upregulation of lysyl oxidase, respectively. Data from the current study illustrate the dynamic nature of physical remodeling of cartilage ECM and elucidate the key mechanotransduction pathway regulating chondrocyte metabolism and osteoarthritic cartilage destruction.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- July 2015
- DOI:
- 10.1073/pnas.1505700112
- Bibcode:
- 2015PNAS..112.9424K