| Purpose:Temporomandibular joint osteoarthritis (TMJOA) is an important subtype of temporomandibular disorders. This study investigated the inflammatory role of stromal cell-derived factor-1 (SDF-1) and C-X-C chemokine receptor-4 (CXCR4) axis and the probable signaling pathway involved in matrix metalloprotease (MMP)-3 and MMP-9 productions stimulated by SDF-1-CXCR4 axis in an experimental rat model of TMJOA.Methods:90,8-week-old, female Wistar rats were randomly distributed into a control group (n=18), a pathologic model group (n=18) and an AMD3100 group (n=54), additionally, the AMD3100 group was distributed into high, middle and low concentration AMD3100 groups (there were 18 Wistar rats in each group). Rats in the pathologic model and AMD3100 groups were established TMJOA model by injected with monosodium iodo-acetate into the upper compartment of TMJ, and rats in the control group were injected with saline for instead. After the establishment of TMJOA model, rats in the AMD3100 goups were injected with various concentrations of AMD3100 every other day for 4 weeks, and the other groups were injected with PBS for instead.4 weeks later, bilateral TMJs were seprated for different detections. Gross inspection, HE staining and Saffrain-O staining were employed for detecting the severity of TMJOA. The relative expressions of SDF-1 mRNA, CXCR4 mRNA, MMP-3 mRNA and MMP-9 mRNA were determined by RT-PCR (Real-time PCR). Immunohistochemistry was employed to detect the expressions of SDF-1, CXCR4, MMP-3 and MMP-9 proteins in the TMJ. Productions of various cytokines were compared, and the protein expressions of p-ERK and MMP-3, p-ERK and MMP-9 in the AMD3100 groups were analyzed by the correlation analysis.Results:The results of gross inspection, HE staining and Saffrain-O staining showed that TMJs in the pathologic model group exhibited obvious TMJOA manifestations, and they were more serious than the AMD3100 goups, additionally, the severity of TMJOA alleviated with the concentrations of AMD3100 in the AMD3100 goups. Compared with the control group, expressions of SDF-O and CXCR4 in the pathologic model group were increased (p< 0.05). Releases of MMP-3, MMP-9, and p-ERK mRNA and proteins were:the pathologic model goup> the AMD3100 goups> the control goup (p< 0.05), moreover, in the AMD3100 groups, with the concentrations of AMD3100 increasing, releases of MMP-3, MMP-9, and p-ERK mRNA and proteins decreased. Additionally, there were strong predictive relations between the expression of p-ERK with MMP-3 (r2= 0.419;/?< 0.001) and with MMP-9 (r2= 0.542;/?< 0.001).Conclusion:The SDF-1/CXCR4 signaling pathway plays a proinflammatory role in experimental TMJOA, and the expressions of SDF-1 and CXCR4 in TMJOA rats significantly increase. The bicyclam derivative AMD3100 can alleviate the severity of experimental TMJOA in a dose dependent manner, and SDF-1/CXCR4 axis may increase the expressions of MMP-3 and MMP-9 through ERK signaling pathway. |
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