Fibroblast-like synovial cell production of extra domain A fibronectin associates with inflammation in osteoarthritis
Abstract 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 (TGFβ)-induced myofibroblast production of extracellular matrix. Fibronectins are an essential part of the ext...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2019-12-01
|
| Series: | BMC Rheumatology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s41927-019-0093-4 |
| _version_ | 1818880320546537472 |
|---|---|
| author | Tue W. Kragstrup Dong H. Sohn Christin M. Lepus Kazuhiro Onuma Qian Wang William H. Robinson Jeremy Sokolove |
| author_facet | Tue W. Kragstrup Dong H. Sohn Christin M. Lepus Kazuhiro Onuma Qian Wang William H. Robinson Jeremy Sokolove |
| author_sort | Tue W. Kragstrup |
| collection | DOAJ |
| description | Abstract 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 (TGFβ)-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 (αSMA) 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 TGFβ but not by TNFα, lipopolysaccharide, or IL-6 (n = 3). ED-A fibronectin co-stained with the myofibroblast marker αSMA 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 TNFα (n = 5). Recombinant ED-A fibronectin increased the production of TNFα 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. |
| first_indexed | 2024-12-19T14:44:06Z |
| format | Article |
| id | doaj.art-a50a41d9eb314ea48a725fd4f7b270d3 |
| institution | Directory Open Access Journal |
| issn | 2520-1026 |
| language | English |
| last_indexed | 2024-12-19T14:44:06Z |
| publishDate | 2019-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Rheumatology |
| spelling | doaj.art-a50a41d9eb314ea48a725fd4f7b270d32022-12-21T20:16:59ZengBMCBMC Rheumatology2520-10262019-12-01311810.1186/s41927-019-0093-4Fibroblast-like synovial cell production of extra domain A fibronectin associates with inflammation in osteoarthritisTue W. Kragstrup0Dong H. Sohn1Christin M. Lepus2Kazuhiro Onuma3Qian Wang4William H. Robinson5Jeremy Sokolove6Department of Immunology and Rheumatology, Stanford UniversityDepartment of Immunology and Rheumatology, Stanford UniversityDepartment of Immunology and Rheumatology, Stanford UniversityDepartment of Immunology and Rheumatology, Stanford UniversityDepartment of Immunology and Rheumatology, Stanford UniversityDepartment of Immunology and Rheumatology, Stanford UniversityDepartment of Immunology and Rheumatology, Stanford UniversityAbstract 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 (TGFβ)-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 (αSMA) 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 TGFβ but not by TNFα, lipopolysaccharide, or IL-6 (n = 3). ED-A fibronectin co-stained with the myofibroblast marker αSMA 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 TNFα (n = 5). Recombinant ED-A fibronectin increased the production of TNFα 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.https://doi.org/10.1186/s41927-019-0093-4OsteoarthritisFibronectinMyofibroblastInflammationArthritisSynovitis |
| spellingShingle | Tue W. Kragstrup Dong H. Sohn Christin M. Lepus Kazuhiro Onuma Qian Wang William H. Robinson Jeremy Sokolove Fibroblast-like synovial cell production of extra domain A fibronectin associates with inflammation in osteoarthritis BMC Rheumatology Osteoarthritis Fibronectin Myofibroblast Inflammation Arthritis Synovitis |
| title | Fibroblast-like synovial cell production of extra domain A fibronectin associates with inflammation in osteoarthritis |
| title_full | Fibroblast-like synovial cell production of extra domain A fibronectin associates with inflammation in osteoarthritis |
| title_fullStr | Fibroblast-like synovial cell production of extra domain A fibronectin associates with inflammation in osteoarthritis |
| title_full_unstemmed | Fibroblast-like synovial cell production of extra domain A fibronectin associates with inflammation in osteoarthritis |
| title_short | Fibroblast-like synovial cell production of extra domain A fibronectin associates with inflammation in osteoarthritis |
| title_sort | fibroblast like synovial cell production of extra domain a fibronectin associates with inflammation in osteoarthritis |
| topic | Osteoarthritis Fibronectin Myofibroblast Inflammation Arthritis Synovitis |
| url | https://doi.org/10.1186/s41927-019-0093-4 |
| work_keys_str_mv | AT tuewkragstrup fibroblastlikesynovialcellproductionofextradomainafibronectinassociateswithinflammationinosteoarthritis AT donghsohn fibroblastlikesynovialcellproductionofextradomainafibronectinassociateswithinflammationinosteoarthritis AT christinmlepus fibroblastlikesynovialcellproductionofextradomainafibronectinassociateswithinflammationinosteoarthritis AT kazuhiroonuma fibroblastlikesynovialcellproductionofextradomainafibronectinassociateswithinflammationinosteoarthritis AT qianwang fibroblastlikesynovialcellproductionofextradomainafibronectinassociateswithinflammationinosteoarthritis AT williamhrobinson fibroblastlikesynovialcellproductionofextradomainafibronectinassociateswithinflammationinosteoarthritis AT jeremysokolove fibroblastlikesynovialcellproductionofextradomainafibronectinassociateswithinflammationinosteoarthritis |