CXCR3 mediates chondrocyte injury through regulating nitric oxide.

OBJECTIVE

As a common joint disease, osteoarthritis exhibits increasing trend in recent years. C-X-C motif chemokine receptor 3 (CXCR3) is a kind of chemokine with the characteristic of recruiting inflammatory cells. Its function in osteoarthritis has not been clarified. This study aims to explore the role of CXCR3 in cartilage injury by affecting unfolded protein response (UPR) pathway.

PATIENTS AND METHODS

The sample was obtained from osteoarthritis patients to test CXCR3 expression by Real-time polymerase chain reaction (PCR). Chondrocyte apoptosis model was established in vitro induced by interleukin 1β (IL-1β) and sodium nitroprusside (SNP). CXCR3 level was downregulated by using siRNA. Cell apoptosis was determined by using transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assay. UPR pathway related factors C/EBP homology protein (CHOP) and glucose regulated protein 78 (GRP78) protein expressions were tested by using Western blot.

RESULTS

CXCR3 protein level significantly increased in osteoarthritis patients (2.66 ± 0.25 vs. 1.00 ± 0.05, p<0.05). CXCR3 siRNA significantly reduced nitrate level in chondrocytes induced by IL-β (35.22 ± 1.76 vs. 17.82 ± 0.89, p<0.05) without affecting cell apoptosis (1.13 ± 0.05 vs. 0.859 ± 0.04, p>0.05). CXCR3 siRNA markedly downregulated nitrate level in chondrocytes (50.63 ± 2.53 vs. 30.63 ± 1.63, p<0.05) and alleviated cell apoptosis induced by SNP (1.98 ± 0.10 vs. 1.25 ± 0.06, p<0.05). UPR pathway C/EBP homology protein (CHOP) and glucose regulated protein 78 (GRP78) participated in the process of chondrocyte apoptosis.

CONCLUSIONS

Endoplasmic reticulum (ER) stress signaling pathway CHOP and GRP78 are involved in CXCR3 receptor attenuating chondrocyte apoptosis induced by SNP.