Fibroblast-like synovial cell production of extra domain A fibronectin associates with inflammation in osteoarthritis. BMC rheumatology Kragstrup, T. W., Sohn, D. H., Lepus, C. M., Onuma, K., Wang, Q., Robinson, W. H., Sokolove, J. 2019; 3: 46


Background: The pathophysiology of osteoarthritis (OA) involves wear and tear, and a state of low-grade inflammation. Tissue repair responses include transforming growth factor beta (TGFbeta)-induced myofibroblast production of extracellular matrix. Fibronectins are an essential part of the extracellular matrix, and injection of fibronectin fragments into rabbit joints is a previously established animal model of OA. Fibronectin containing the ED-A domain is currently being used as drug delivery target in the development of anti-inflammatory drugs (e.g. Dekavil).Methods: In this study, samples of synovial membrane were obtained from patients with knee OA undergoing joint replacement surgery. Immunostaining for ED-A fibronectin and the myofibroblast marker alpha smooth muscle actin (alphaSMA) was performed on fibroblast-like synovial cells (FLS) and synovial membranes. RAW 264.7 macrophages were incubated with recombinant ED-A fibronectin.Results: The staining of ED-A fibronectin in OA FLS was increased by TGFbeta but not by TNFalpha, lipopolysaccharide, or IL-6 (n=3). ED-A fibronectin co-stained with the myofibroblast marker alphaSMA in both the OA FLS (n=3) and in the OA synovial membranes (n=8). ED-A fibronectin staining was associated with both number of lining layer cells (rho=0.85 and p=0.011) and sublining cells (rho=0.88 and p=0.007) in the OA synovium (n=8), and co-distributed with TNFalpha (n=5). Recombinant ED-A fibronectin increased the production of TNFalpha by RAW 264.7 macrophages (n=3).Conclusions: The disease process in OA shares features with the chronic wound healing response. Our findings support utilizing ED-A fibronectin for drug delivery or therapeutic targeting to reduce pro-inflammatory responses in OA.

View details for DOI 10.1186/s41927-019-0093-4

View details for PubMedID 31819923