1 Introduction
Osteoarthritis (OA) is a common joint disease with high rate of incidence and wide coverage in the elderly population, which causes a severe economic burden on families and society 1,2. Current research has shown that OA is characterized by cartilage degradation, underlying bone remodeling, and synovial inflammation3. Several risk factors, such as age, gender, obesity and genetics, may affect the development of OA 2,4. Nevertheless, the underlying molecular mechanism among OA remains obscure.
Increasing evidence suggests that low-grade inflammation is a key mediator of the pathogenesis of OA 5. Chondrocytes, as the only cellular component of cartilage, play a central role in the synthesis of cartilage matrix. OA is defined as the accumulation of degenerative factors leading to the decease of chondrocytes and the degradation of extracellular matrix (ECM). During OA, pro-inflammatory factors, such as IL-1β, TNF-α, trigger a series of pathogenic reactions of chondrocytes, promoting inflammation, senescence, and apoptosis6. Current treatment is aimed at relieving the symptoms of OA but cannot slow down disease progression. Therefore, it is necessary to further facilitate identification of emerging pharmaceutical therapies.
Empagliflozin (Empa), a selective inhibitor of sodium-glucose cotransporter-2 (SGLT2), lowers blood sugar by reducing glucose reabsorption in the renal tubules. Various studies showed favorable effects of Empa on glycaemic improvement, body weight, blood pressure, arterial stiffness, and endothelial function 7-9. In recent years, Empa has been reported to regulate macrophage polarity and exert anti-inflammatory effects 10. Also, Empa has hepatic protective effect against cholestatic liver injury via its anti-oxidant and anti-inflammatory properties 11. However, the effect of Empa on inflammation and senescence in OA has not been reported yet
In our study, we hypothesized that Empa might inhibit inflammation in chondrocytes during the process of OA. We concentrated on the anti-inflammatory effect of Empa on chondrocytes and the underlying mechanism. We hope that our study will provide a new therapeutic approach for the treatment of OA in the future.