Proinflammatory cytokines and lipopolysaccharides up regulate MMP-3 and MMP-13 production in Asian elephant (Elephas maximus) chondrocytes: attenuation by anti-arthritic agents

Abstract

BackgroundOsteoarthritis (OA), the most common form of arthritic disease, results from destruction of joint cartilage and underlying bone. It affects animals, including Asian elephants (Elephas maximus) in captivity, leading to joint pain and lameness. However, publications regarding OA pathogenesis in this animal are still limited. Therefore, this study aimed to investigate the effect of proinflammatory cytokines, including interleukin-1 beta (IL-1β), IL-17A, tumor necrosis factor-alpha (TNF-α), and oncostatin M (OSM), known mediators of OA pathogenesis, and lipopolysaccharides on the expression of cartilaginous degrading enzymes, matrix metalloproteinase (MMP)-3 and MMP-13, in elephant articular chondrocytes (ELACs) cultures. Anti-arthritic drugs and the active compounds of herbal plants were tested for their potential attenuation against overproduction of these enzymes.ResultsAmong the used cytokines, OSM showed the highest activation of MMP3 and MMP13 expression, especially when combined with IL-1β. The combination of IL-1β and OSM was found to activate phosphorylation of the mitogen-activated protein kinase (MAPK) pathway in ELACs. Lipopolysaccharides or cytokine-induced expressions were suppressed by pharmacologic agents used to treat OA, including dexamethasone, indomethacin, etoricoxib, and diacerein, and by three natural compounds, sesamin, andrographolide, and vanillylacetone.ConclusionsOur results revealed the cellular mechanisms underlying OA in elephant chondrocytes, which is triggered by proinflammatory cytokines or lipopolysaccharides and suppressed by common pharmacological or natural medications used to treat human OA. These results provide a more basic understanding of the pathogenesis of elephant OA, which could be useful for adequate medical treatment of OA in this animal.

Dexamethasone-loaded thermo-sensitive hydrogel attenuates osteoarthritis by protecting cartilage and providing effective pain relief

“…Expressions of MMPs and ADAMTSs are both elevated in OA cartilage and activities of both MMPs and ADAMTSs are positively associated with cartilage degradation (29,30). Matrix-degrading enzymes secreted by chondrocytes (e.g., MMPs and ADAMTSs) degrade the extracellular matrix (ECM) of cartilage; these degraded ECM fragments further induce synovial inflammation and inflammatory factor generation, eventually resulting in cartilage damage and OA progression (31). In the ECM of OA cartilage, MMP-13 is the main degrading enzyme for collagen, and ADAMTS-5 is the major degrading proteinase for aggrecan (32,33).…”

Pharmacokinetic–pharmacodynamic modeling analysis and anti‐inflammatory effect of Wangbi capsule in the treatment of adjuvant‐induced arthritis

“…The increase of PGE 2 in vivo was associated with vasodilation, pain, redness and swelling of joints, cartilage corrosion and fluid extravasation (Fattahi & Mirshafiey, 2012). In addition, the increase of IL-1β can stimulate synovial fibroblasts, chondrocytes and osteoclasts to produce tissue-damaging matrix metalloprotease (MMP), leading to bone loss (Sirikaew et al, 2019). Numerous published reports have shown that osthole, cimifugin, 5-O-methylvisammioside, albiflorin, paeoniflorin and icariin, the active components of WBC, can directly or indirectly regulate nuclear factor kappa-B or other signal pathways and reduce the contents of inflammatory cytokines IL-1β and PGE 2 (Liu et al, 2020;Xu et al, 2018).…”

Safflower Seed Extract Attenuates the Development of Osteoarthritis by Blocking NF-κB Signaling

“…Therefore, mouse chondrocytes can be used to mimic experimental OA in vitro. IL-1β treatment of chondrocytes upregulates the expression of catabolic factors, including MMP3 and MMP13 [ 42 , 43 , 44 , 45 ]. These proteases act as collagenase and promote the degradation of type II collagen, after cartilage destruction [ 30 ].…”

“…These proteases act as collagenase and promote the degradation of type II collagen, after cartilage destruction [ 30 ]. Clinical data have shown that MMP3 and MMP13 are highly expressed in the cartilage of patients with arthritis, resulting in OA progression [ 44 ]. In the present study, safflower seed extract suppressed the expression of MMP3, MMP13, and ADAMTS5 induced by IL-1β stimulation in chondrocytes.…”