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

• Published in: BMC veterinary research Vol. 15; no. 1; p. 419
• Main Authors: Sirikaew, Nutnicha, Chomdej, Siriwadee, Tangyuenyong, Siriwan, Tangjitjaroen, Weerapongse, Somgird, Chaleamchat, Thitaram, Chatchote, Ongchai, Siriwan
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 21.11.2019; BioMed Central; BMC
• Subjects: active ingredients; andrographolide; animal diseases; Animals; Anti-Inflammatory Agents - pharmacology; Antiarthritic agents; Arthralgia; Arthritis; Asiatic elephant; captive animals; Captivity; cartilage; Cartilage diseases; Cells, Cultured; Chondrocytes; Chondrocytes - drug effects; Chondrocytes - metabolism; Collagenase 3; Cytokines; Cytokines - toxicity; Development and progression; Dexamethasone; Diseases; Drug dosages; Elephants - metabolism; Elephas maximus; Enzymes; Etoricoxib; Gene Expression Regulation, Enzymologic - drug effects; humans; IL-1β; Indomethacin; Inflammation; Interleukin 1; interleukin-17; interleukin-1beta; Interleukins; Kinases; lameness; Lipopolysaccharides; Lipopolysaccharides - toxicity; MAP kinase; Matrix metalloproteinase; Matrix Metalloproteinase 13 - genetics; Matrix Metalloproteinase 13 - metabolism; Matrix Metalloproteinase 3 - genetics; Matrix Metalloproteinase 3 - metabolism; medical treatment; Metalloproteinase; metalloproteinases; mitogen-activated protein kinase; Mitogens; MMP-13; MMP-3; Oncostatin M; Osteoarthritis; pain; Pathogenesis; Phosphorylation; Proinflammatory cytokines; Protein kinase; Proteins; Signal transduction; Stromelysin 1; Tumor necrosis factor; tumor necrosis factor-alpha; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Up-Regulation - drug effects; United Kingdom; MMP-13; Proinflammatory cytokines; Osteoarthritis; Elephas maximus; MMP-3
• DOI: 10.1186/s12917-019-2170-8
• ISSN: 1746-6148

Osteoarthritis (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. Among 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. Our 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.