Expression of LOXs and MMP-1, 2, 3 by ACL Fibroblasts and Synoviocytes Impact of Coculture and TNF-α

Abstract

This study aims to confirm the effects of synoviocytes (SCs) on regulating lysyl oxidases (LOXs) and matrix metalloproteinase (MMP)-1, 2, 3 in the normal and injured anterior cruciate ligament (ACL) fibroblasts response to tumor necrosis factor-α(TNF-α). The gene and protein expression levels of LOXs and MMP-1, 2, 3 in SCs cocultured ACL fibroblasts (ACLfs) induced by TNF-α and mechanical injury were analyzed by real-time polymerase chain reaction (PCR) and western bolting; the MMP-2 activity were analyzed by zymography. The results exhibited that TNF-α alone slightly downregulated the expressions of LOXs and upregulated the expression of MMP-1, 2, 3 in both normal and injured ACL fibroblasts. The decrease of LOXs and increase of MMP-1, 2, 3 in ACLfs response to TNF-α were further promoted by coculture. Taken together, these results show for the first time that the crosstalk between ACLfs and SCs could modulate the LOXs and MMP-1, 2, 3 synthesis in ACLfs in the presence of TNF-α. Accumulation of MMPs in the isolated fluid-containing space not only disrupts the balance of ACL healing, but also increases cartilage degradation and accelerates osteoarthritis (OA) in injured joint. Based on this mechanism, targeting inhibition of MMPs could provide a promising therapeutic strategy for acute ligament injury.

Proteomic Analysis of Synovial Fibroblasts and Articular Chondrocytes Co-Cultures Reveals Valuable VIP-Modulated Inflammatory and Degradative Proteins in Osteoarthritis

“…Several studies have noted increased MMP2 levels in cartilage [ 98 , 125 , 126 , 127 , 128 ], serum [ 129 ], synovial fluid [ 130 , 131 , 132 , 133 ], as well as in the synovium and pannus-like tissue in OA [ 128 , 134 ]. This increased expression was also detected in SF from RA and OA patients [ 135 , 136 ], in synoviocytes co-cultured with fibroblasts [ 137 ] and platelets [ 130 ], as well as in AC co-cultured with subchondral bone osteoblasts in OA [ 138 ]. Consequently, MMP2 is defined as a potential biomarker for OA [ 139 , 140 , 141 ], and is positively correlated to histopathology severity in OA cartilage [ 142 ].…”

Nobiletin exhibits potent inhibition on tumor necrosis factor alpha‐induced calcification of human aortic valve interstitial cells via targeting ABCG2 and AKR1B1

“…Based on this, we explored whether NBT could effectively inhibit hVICs calcification and used transcriptome sequencing and molecular docking analysis to explore the signaling mechanisms and protein targets. The acute inflammatory response mimicked by TNF‐α is widely used in inflammatory models of different originated cells (Wang, Hu, et al, ; Wang, Chi, et al, ; Xie et al, ; Xie et al, ). For the calcification model of hVICs, TNF‐α has been shown to have a significant effect on the development of calcification phenotypes in the cells isolated from patients with CHVD and is therefore considered to be an ideal model of valvular calcification in vitro (Yu et al, ).…”

Sodium Monoiodoacetate Dose-Dependent Changes in Matrix Metalloproteinases and Inflammatory Components as Prognostic Factors for the Progression of Osteoarthritis

“…* denotes p < 0.05; ** denotes p < 0.01; *** denotes p < 0.001 vs. intact animals. (Wang et al, 2019). In rheumatoid arthritis (RA) synovial fibroblasts, MMP-2 and MMP-9 contribute to cell survival, proliferation and migration.…”