C-X-C chemokine receptor type 4 antagonist delays the degeneration of articular cartilage in guinea pigs

doi:10.12307/2022.475

Abstract

Abstract: BACKGROUND: Studies have shown that the stromal cell-derived factor 1/C-X-C chemokine receptor type 4 signaling pathway plays an important role in the occurrence and development of osteoarthritis.
OBJECTIVE: To explore the effect of C-X-C chemokine receptor type 4 antagonist on the degeneration of articular cartilage in vivo.
METHODS: Ninety-six 6-month-old male Hartley guinea pigs were randomly divided into four groups, namely, TN14003 treatment, T140 treatment, AMD3100 treatment group, and blank control group (n=24 per group). Except for the blank control group without any treatment, in the rest three groups, Alzet micro-pumps were directly implanted and fixed under the skin of the back of the guinea pigs, followed by daily injection of TN14003, T140, and AMD3100 drugs at a concentration of 180 mg/L, respectively. After 12 weeks of interventions, the articular cartilage of the knee joint was taken out from guinea pigs for hematoxylin-eosin staining, Safranin-fast green staining, and modified Mankin histological scoring. Immunohistochemical staining was used to detect the expression levels of interleukin-1 and tumor necrosis factor-α.
RESULTS AND CONCLUSION: Hematoxylin-eosin staining and Safranin-fast green staining showed that the degree of cartilage degeneration in the TN14003 treatment group was significantly delayed, with the highest Mankin score, followed by T140 treatment group, AMD3100 group and blank control group in turn. There were significant differences in the Mankin scores between the experimental groups (P < 0.05). The results of immunohistochemical staining analysis showed that the positive expression of interleukin-1 and tumor necrosis factor-α in each experimental group was lower than that of the blank control group, among which the expression was lowest in the TN14003 treatment group (P < 0.05). To conclude, these three kinds of C-X-C chemokine receptor type 4 antagonists can all block the stromal cell-derived factor 1/C-X-C chemokine receptor type 4 signaling pathway in vivo, reduce the expression levels of interleukin-1 and tumor necrosis factor-α, and delay cartilage degeneration, among which TN14003 has the best effects.

Key words: osteoarthritis, stromal cell-derived factor 1, C-X-C chemokine receptor type 4, signaling pathway, C-X-C chemokine receptor 4 antagonist, cartilage degeneration, guinea pig

CLC Number:

He Lu, Li Yanlin, Meng Xuhan, Wang Guoliang, Yang Tengyun, Liao Xinyu, Zhou Xiaoxiang, Yang Guang. C-X-C chemokine receptor type 4 antagonist delays the degeneration of articular cartilage in guinea pigs[J]. Chinese Journal of Tissue Engineering Research, 2022, 26(14): 2150-2154.

Figures/Tables 6

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