TN14003 attenuates cartilage degeneration by targeted blocking of the SDF-1/CXCR4 signaling pathway in knee osteoarthritis
Abstract In order to investigate the effect of TN14003 and its mechanism on cartilage degeneration in vitro and in vivo. P1 chondrocytes isolated from cartilage tissues of OA patients who underwent total knee arthroplasty were randomly assigned to blank control group, TN14003 group, T140 group, and AMD3100 group in vitro. Each group cells were cultured for 1, 2, 4, 6, 8, 10 days. Cell morphology were observed under inverted phase-contrast microscope and examined using MTT assay, flow cytometry, ELISA (MMPs in the chondrocyte medium) and quantitative real-time PCR (mRNA expressions of Col II and ACAN). Moreover, 96 male Hartley guinea pigs with spontaneous OA were randomly assigned to examine the effect of TN14003, T140, and AMD3100 in vivo. After 12 weeks, guinea pigs were sacrificed, the knee articular cartilage histopathology was analyzed. No difference in morphology, proliferation rate and apoptosis among four groups (P > 0.05). The content of MMP-3 and MMP-13, mRNA expression levels of ACAN and Col II were significantly lower in TN14003 group compared with other groups (P < 0.05). TN14003 had stronger effect in decreasing cartilage degeneration compared with T140 and AMD3100 in vivo. TN14003 could effective targeted to prevention and treatment of OA.