Abstract
BackgroundIntra-articular administration of stanozolol has shown promising results by improving the clinical management of lameness associated with naturally-occurring osteoarthritis (OA) in horses, and by decreasing osteophyte formation and subchondral bone reaction in sheep following surgically induced OA. However, there is limited evidence on the anti-inflammatory and modulatory properties of stanozolol on articular tissues. The objective of the current study was to evaluate the effects of stanozolol on chondrocyte viability and gene expression in normal equine chondrocytes and an inflammatory in vitro system of OA (interleukin-1β (IL-1β) treated chondrocytes).ResultsChondrocytes from normal metacarpophalangeal joints of skeletally mature horses were exposed to four treatment groups: (1) media only (2) media+IL-1β (3) media+IL-1β + stanozolol (4) media+stanozolol. Following exposure, chondrocyte viability and the expression of catabolic, anabolic and structural genes were determined. General linear models with Dunnet’s comparisons with Bonferroni’s adjustment were performed. Cell viability was similar in all groups. Stanozolol treatment reduced gene expression of MMP-13, MMP-1, IL-6 and COX-2 in both normal and IL-1β treated chondrocytes. Stanozolol treatment reduced ADAMTS4 gene expression in normal chondrocytes. Stanozolol reduced the expression of COL2A1.ConclusionsThe current study demonstrates stanozolol has chondroprotective effects through downregulation of genes for pro-inflammatory/catabolic cytokines and enzymes associated with OA. However, there is no evidence of increased cartilage stimulation through upregulation of the anabolic and structural genes tested.
Highlights
Intra-articular administration of stanozolol has shown promising results by improving the clinical management of lameness associated with naturally-occurring osteoarthritis (OA) in horses, and by decreasing osteophyte formation and subchondral bone reaction in sheep following surgically induced OA
Stanozolol reduces catabolic gene expression There was a statistically significant increase in the expression of Matrix metalloproteinase (MMP)-13, MMP-1, Interleukin 6 (IL-6), ADAMTS4 and cyclooxygenase 2 (COX-2) Messenger ribonucleic acid (mRNA) expression in chondrocytes treated with IL-1β only compared to media only (P < 0.001)
When comparing both groups with IL-1β treated chondrocytes, there was a significant downregulation of MMP13 (P < 0.001), MMP-1 (P < 0.03), IL-6 (P < 0.001) and COX-2 (P < 0.001) expression in chondrocytes exposed to IL-1β and stanozolol compared to chondrocytes exposed to IL-1β alone
Summary
Intra-articular administration of stanozolol has shown promising results by improving the clinical management of lameness associated with naturally-occurring osteoarthritis (OA) in horses, and by decreasing osteophyte formation and subchondral bone reaction in sheep following surgically induced OA. The objective of the current study was to evaluate the effects of stanozolol on chondrocyte viability and gene expression in normal equine chondrocytes and an inflammatory in vitro system of OA (interleukin-1β (IL-1β) treated chondrocytes). Osteoarthritis (OA) is caused by a combination of biomechanical and biochemical changes in the joint that include synovium and subchondral bone abnormalities, resulting in cartilage degeneration [1]. Cartilage repair is mediated by the balance between chondrocyte gene expression of catabolic and anabolic genes [4, 5]. The most important mediator of cartilage degeneration is interleukin-1 (IL-1) [5, 6] and it has been reported that low innate production of IL-1β and IL-6 is associated with the absence of OA in old age [7].
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