Empagliflozin ameliorated chondrocytes inflammation, catabolism and
senescence and osteoarthritis via suppressing the nuclear factor kappa-B
signal pathway.
Abstract
Background Extracellular matrix (ECM) degradation, chondrocyte
inflammation, and cellular senescence contribute to the pathology of
osteoarthritis (OA). Empagliflozin, a selective inhibitor of
sodium-glucose cotransporter-2 (SGLT2), has been reported to show the
anti-inflammatory properties in several conditions. However, whether
empagliflozin can be used to improve OA is still unknown. Methods The
protective effects and underlying mechanism of empagliflozin in OA were
investigated in vitro and in vivo. Cell viability, catabolic markers,
inflammatory mediators, cellular senescence level, cartilage
degeneration were evaluated by CCK-8 assay, safranine O staining, ELISA,
real-time PCR, western blot, β-galactosidase Staining, and histological
analysis. Results We found that empagliflozin significantly
downregulated the expression of catabolic enzymes (MMP9 and MMP13), and
decreased the expression of inflammatory mediators (NO, PGE2, IL-6,
COX2, and INOS), and reduced the cellular senescence level in
IL-1β-treated chondrocytes by inhibiting the nuclear factor kappa-B
(NF-κB) signaling pathway. What’s more, empagliflozin prevented
cartilage degeneration in DMM-induced OA mice model with significant
lower OARSI grade. Conclusion Our findings reveal that empagliflozin
inhibited chondrocytes ECM degradation, inflammation and cellular
senescence in vitro and prevented cartilage degeneration in vivo by
suppressing NF-κB signal pathway, indicating a therapeutic potential in
OA treatment.