Ginsenoside Compound K Ameliorates Osteoarthritis by Inhibiting the Chondrocyte Endoplasmic Reticulum Stress-Mediated IRE1α-TXNIP-NLRP3 Axis and Pyroptosis

Osteoarthritis
(OA) is a common joint disease, and studies have
reported that the endoplasmic reticulum stress (ERS) in chondrocytes
caused by the cartilage tissue damage could mediate the activation
of Nod-like receptor protein 3 (NLRP3) inflammasomes through inositol-requiring
enzyme 1 alpha (IRE1α) and thioredoxin interacting protein (TXNIP).
Ginsenoside compound K (CK) has an inhibitory effect on IRE1α
activation. However, the role of IRE1α-TXNIP and its interaction
with CK are still unclear. In this study, we examined the role and
mechanism of action of CK in OA. We found that CK ameliorated OA and
ERS in IL-1β-treated chondrocytes and a monoiodoacetate-induced
rat OA model. The effect of CK on inflammation, pyroptosis, and ERS
was blocked by the ERS inducer tunicamycin. In conclusion, CK hindered
OA progression by inhibiting the ERS-IRE1α-TXNIP-NLRP3 axis.
Overall, our data indicate that CK could be useful in the treatment
of OA and other chronic inflammatory diseases.