| First Author | Almonte-Becerril M | Year | 2018 |
| Journal | PLoS One | Volume | 13 |
| Issue | 6 | Pages | e0198559 |
| PubMed ID | 29870552 | Mgi Jnum | J:262826 |
| Mgi Id | MGI:6161511 | Doi | 10.1371/journal.pone.0198559 |
| Citation | Almonte-Becerril M, et al. (2018) Genetic abrogation of the fibronectin-alpha5beta1 integrin interaction in articular cartilage aggravates osteoarthritis in mice. PLoS One 13(6):e0198559 |
| abstractText | The balance between synthesis and degradation of the cartilage extracellular matrix is severely altered in osteoarthritis, where degradation predominates. One reason for this imbalance is believed to be due to the ligation of the alpha5beta1 integrin, the classic fibronectin (FN) receptor, with soluble FN fragments instead of insoluble FN fibrils, which induces matrix metalloproteinase (MMP) expression. Our objective was to determine whether the lack of alpha5beta1-FN binding influences cartilage morphogenesis in vivo and whether non-ligated alpha5beta1 protects or aggravates the course of osteoarthritis in mice. We engineered mice (Col2a-Cre;Fn1RGE/fl), whose chondrocytes express an alpha5beta1 binding-deficient FN, by substituting the aspartic acid of the RGD cell-binding motif with a glutamic acid (FN-RGE). At an age of 5 months the knee joints were stressed either by forced exercise (moderate mechanical load) or by partially resecting the meniscus followed by forced exercise (high mechanical load). Sections of femoral articular knees were analysed by Safranin-O staining and by immunofluorescence to determine tissue morphology, extracellular matrix proteins and matrix metalloproteinase expression. The articular cartilage from untrained control and Col2a-Cre;Fn1RGE/fl mice was normal, while the exposure to high mechanical load induced osteoarthritis characterized by proteoglycan and collagen type II loss. In the Col2a-Cre;Fn1RGE/fl articular cartilage osteoarthritis progressed significantly faster than in wild type mice. Mechanistically, we observed increased expression of MMP-13 and MMP-3 metalloproteinases in FN-RGE expressing articular cartilage, which severely affected matrix remodelling. Our results underscore the critical role of FN-alpha5beta1 adhesion as ECM sensor in circumstances of articular cartilage regeneration. |
