| ABSTRACT Objective: To study the change of joint synovium in the early stage of knee osteoarthritis (OA) through the TLR4/NF-κB pathway in rats.
Methods: 18 male SD rats about 200 g were randomly divided into 2 groups (control group, model group). The knee OA model group was established using modified Hulth method. The control group was not treated. Synovial tissue and serum was extracted at 4 d, and 21 d after operation. The expression of CD14, TLR-4, IL-1β, TNF-a, ADAMTS-4, or MMP-13 mRNA was detected by real-time PCR, respectively. NF-κB p65 protein was detected by Western blot; serum concentrations of haluronic acid (HA), or N-propeptide of type III procollagen (PIIINP) was detected by Elisa.
Results: Compared with the control group, the expression of CD14 mRNA in knee OA model was statistically different at 4 d ((1.000±0.02) vs. (1.156±0.02); P<0.01)) and 21 d ((1.001±0.06) vs. (3.525±0.16); P<0.01)). After modeling, the expression of TLR4 mRNA, IL-1β mRNA and TNF-a mRNA was increased with time, and was statistically significant at 21 d ((1.002±0.08) vs. (3.016±0.22); P<0.01)), ((1.002±0.08±0.08) vs. (2.065±0.11); P<0.01)), ((1.001±0.05) vs. (2.930±0.08)；P<0.01)), respectively. The MMP13 mRNA in the knee OA model was significantly expressed at 21 d ((1.000±0.03) vs. (5.560±0.49) ；P<0.01)), and ADAMTS-4 mRNA expression was statistically different at 4 d ((1.001±0.05) vs. (1.147±0.42); P<0.01)) and 21 d ((1.001±0.05) vs. (2.349±0.09); P<0.01)). The protein of NF-κB p65 in model group was higher than that in the control group, the difference was observed at 4 d ((0.639±0.07) vs. (0.356±0.03) ；P<0.01)) and 21 d ((0.425±0.00) vs. (0.139±0.01) ；P<0.01)). After modeling, the concentration of PIIINP or HA was higher than that in the control group, which was statistically significant at 4 d ((112.746±3.39) vs. (146.463±0.44) ；P<0.05) ； (0.047±0.00) vs. (0.048±0.00) ；P<0.05)) ，but no statistically significant at 21 d (P＞0.05), and the concentration of PIIINP or HA decreased with time.
Conclusion: The NF-κB pathway triggers synovial inflammatory secretion CD14, TLR-4, IL-1β, TNF-a, ADAMTS-4, MMP-13, PIIINP and HA through CD14/TLR4 activation to mediate knee OA. |
