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.