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.
Highlights
Osteoarthritis (OA), the most common form of arthritic disease, results from destruction of joint cartilage and underlying bone
Proinflammatory cytokines induced upregulation of MMP3 and MMP13 expression in elephant articular chondrocytes (ELACs) culture Treatment with oncostatin M (OSM) alone resulted in a slight increase in MMP3 mRNA levels and a marked elevation of MMP13 levels
The results of treatments with combined cytokines demonstrate that OSM combined with IL-1β dramatically increased the expression of both MMP3 and MMP13, whereas OSM combined with Tumor necrosis factor-alpha (TNF-α) slightly induced the expression of MMP13 but not that of MMP3
Summary
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. This study aimed to investigate the effect of proinflammatory cytokines, including interleukin-1 beta (IL1β), 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. Excessive body weight along with the captive environment and trained behaviors are critical factors of OA pathogenesis in elephants [3, 4] These factors disturb the equilibrium between the synthesis and degradation of the extracellular matrix (ECM) by chondrocytes, leading to further degradation of the ECM by matrix-degrading enzymes, especially matrix metalloproteinases (MMPs) [5]. In OA pathogenesis, cytokine-induced signal transduction involves the activation of several pathways, including those of the mitogen-activated protein kinase (MAPK) family [20]
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