Abstract
Osteoarthritis (OA) is a whole-joint disease with extremely high prevalence. In all treatment approaches of OA, blocking the degradation of the cartilage extracellular matrix is an important treatment. In OA, overexpression of derivative enzymes leads to excessive catabolism and reduced synthesis of cartilage including type II collagen and aggrecan, which results in irreversible destruction of the joint. SOX9 is a transcription factor that regulates the synthesis of type II collagen and aggrecan and is significantly downregulated in OA. GPR120 has been reported to affect the pathophysiology of OA. In this study, we used the GPR120 agonist GW9508 and TUG891 in ATDC5 chondrocytes exposed to interleukin (IL)-1β to investigate the involvement of GPR120 in SOX9-mediated expression of type II collagen and aggrecan. Our findings show that agonism of GPR120 can reduce inflammation by inhibiting the expression of IL-6 and IL-8 induced by IL-1β. We also show that GW9508 and TUG891 rescue the expression of type II collagen and aggrecan by preventing the reduction of SOX9 expression. Additionally, we demonstrate that the effects of GW9508 on SOX9 expression are mediated through CREB and that GPR120 is indeed required for this effect. Thus, agonism of GPR120 by GW9508 might be a potential therapeutic strategy to halt or prevent cartilage degradation.
Highlights
Osteoarthritis (OA) is a common debilitating joint disease most often observed among the elderly
We used the GPR120 agonist GW9508 and TUG891 in ATDC5 chondrocytes exposed to interleukin (IL)-1β to investigate the involvement of GPR120 in SOX9mediated expression of type II collagen and aggrecan
The present study provides evidence of the involvement of GPR120 in mediating IL-1β-induced destruction of the articular extracellular matrix in ATDC5 chondrocytes
Summary
Osteoarthritis (OA) is a common debilitating joint disease most often observed among the elderly. Multifarious factors contribute to an increased risk of OA, such as injury, obesity, genetics, diet, and age, among others. Age is considered the primary risk factor. As the average age of the global population increases, so shall the incidence of this painful and costly disease [1, 2]. The main features of OA include excessive catabolism of articular cartilage, inflammation, chondrocyte senescence, oxidative stress, and alterations in the form and function of bone and cartilage tissues [3, 4]. Joint replacement is the go-to treatment for end-stage OA, but especially in elderly patients, surgical intervention can carry additional risks [4]. It is of ample importance to develop preventative therapeutic strategies and non-invasive treatment options against OA
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