Chinese Journal of Tissue Engineering Research ›› 2021, Vol. 25 ›› Issue (5): 668-673.doi: 10.3969/j.issn.2095-4344.2996

Previous Articles     Next Articles

Delaying cartilage degeneration by regulating the expression of aquaporins in rats with knee osteoarthritis

Liu Xin1, Yan Feihua2, Hong Kunhao1   

  1. 1Department of Orthopedics, Guangdong Second Traditional Chinese Medicine Hospital, Guangzhou 510405, Guangdong Province, China; 2Department of Orthopedics, First People’s Hospital of Kashi, Kashi 844000, Xinjiang Uygur Autonomous Region, China
  • Received:2020-04-03 Revised:2020-04-14 Accepted:2020-05-20 Online:2021-02-18 Published:2020-11-27
  • Contact: Liu Xin, Department of Orthopedics, Guangdong Second Traditional Chinese Medicine Hospital, Guangzhou 510405, Guangdong Province, China
  • About author:Liu Xin, MD, Associate chief physician, Department of Orthopedics, Guangdong Second Traditional Chinese Medicine Hospital, Guangzhou 510405, Guangdong Province, China
  • Supported by:
    Guangdong Provincial Special Fund for Science and Technology Innovation Strategy, No. 2018YJ035

Abstract: BACKGROUND: Down-regulation of aquaporins (AQPs) can delay cartilage degeneration in knee osteoarthritis, but its specific mechanism is undefined.
OBJECTIVE: To investigate the effect of p38 MAPK signaling pathway regulating AQP expression on cartilage degeneration in a rat model of knee osteoarthritis. 
METHODS: Sixty Sprague-Dawley rats were randomly divided into sham operation group (sham), model group, SB203580 low concentration group (SB203580-L,    7.5 mg/kg) and high concentration group (SB203580-H, 30 mg/kg), with 15 rats in each group. The modified Hulth method was used to construct the rat model of knee osteoarthritis. In the sham group, the joint cavity was only opened from the medial side of the right knee joint, without damage to the ligament and meniscus, and with preservation of the articular cartilage surface. Intraperitoneal injection of SB203580 with different concentrations was started at 1 week after surgery, once per week, for 8 weeks in total. The degree of knee joint swelling was measured. The pathological changes of cartilage tissue were observed by hematoxylin-eosin staining, and graded by the Mankin’s score. The expression levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-13 (MMP-13) in synovial tissue were detected by ELISA. The AQP1, AQP3 mRNA levels in cartilage tissue were detected by RT-PCR, and the protein levels of AQP1, AQP3, cleaved caspase-3, Bax, Bcl-2, p38MAPK and p-p38MAPK in cartilage tissue were detected by western blot. An approval for this study was obtained from the Animal Experimental Ethics Committee of Guangdong Second Traditional Chinese Medicine Hospital With an approval No. 20180125004
RESULTS AND CONCLUSION: Compared with the sham group, the rats in the model group had severe cartilage injury, the Mankin’s score and the degree of joint swelling were increased significantly (P  < 0.05). Compared with the sham group, the levels of IL-1β, TNF-α and MMP-13 in synovial tissues, the cleaved caspase-3, Bax, and p-p38MAPK protein expression levels in chondrocytes, the mRNA and protein expression levels of AQP1 and AQP3 all increased significantly in the model group (P  < 0.05), whereas the expression level of Bcl-2 protein decreased significantly (P  < 0.05). Compared with the model group, the cartilage injury of rats in the SB203580-H group was improved significantly (P  < 0.05); the Mankin’s score and the degree of joint swelling were decreased significantly (P  < 0.05); the levels of IL-1β, TNF-α and MMP-13 in synovial tissues, the cleaved caspase-3, Bax, and p-p38MAPK protein expression levels in chondrocytes, and the mRNA and protein expression levels of AQP1 and AQP3 all decreased significantly (P  < 0.05), whereas the expression level of Bcl-2 protein increased significantly (P  < 0.05). There was no significant difference between the SB203580-L group and model group (P > 0.05). Therefore, blocking the p38MAPK signaling pathway is deduced to delay the degeneration of articular cartilage in knee osteoarthritis by inhibiting the expression of AQP1 and AQP3.

Key words: bone, cartilage, degeneration, osteoarthritis, knee joint, pathway, protein, mRNA

CLC Number: