Chinese Journal of Tissue Engineering Research ›› 2019, Vol. 23 ›› Issue (23): 3609-3772.doi: 10.3969/j.issn.2095-4344.1304

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Differences in the expression of related degrading enzymes in joint fluids of different stages of osteoarthritis

Wang Haiying1, 2, Ding Xiao1, 2, Yang Li3, Han Fei1, 2, Pu Peidong1, 2, Ma Qingyuan1, 2, Shi Chenhui1, Wang Weishan1   

  1. 1Department of Orthopedics, the First Affiliated Hospital of the Medical College, Shihezi University, Shihezi 832008, Xinjiang Uygur Autonomous Region, China; 2Medical College, Shihezi University, Shihezi 832008, Xinjiang Uygur Autonomous Region, China; 3Department of Pharmacy, Beijing Road Clinical Department, General Hospital of Xinjiang Military Region of Chinese PLA, Urumqi 830000, Xinjiang Uygur Autonomous Region, China
  • Received:2019-02-22 Online:2019-08-18 Published:2019-08-18
  • Contact: Wang Weishan, Chief physician, Professor, Master’s supervisor, Department of Orthopedics, the First Affiliated Hospital of the Medical College, Shihezi University, Shihezi 832008, Xinjiang Uygur Autonomous Region, China Corresponding author: Shi Chenhui, Chief physician, Professor, Doctoral supervisor, Department of Orthopedics, the First Affiliated Hospital of the Medical College, Shihezi University, Shihezi 832008, Xinjiang Uygur Autonomous Region, China
  • About author:Wang Haiying, Master candidate, Department of Orthopedics, the First Affiliated Hospital of the Medical College, Shihezi University, Shihezi 832008, Xinjiang Uygur Autonomous Region, China; Medical College, Shihezi University, Shihezi 832008, Xinjiang Uygur Autonomous Region, China
  • Supported by:

    the National Natural Science Foundation of China, No. 81660374 and 81772407 (both to SCH); the Youth Science and Technology Innovation Leadership Program of the Corps, No. 2016BC001 (to WWS)

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Abstract:

BACKGROUND: At present, there are many studies on the degrading enzymes in synovial membrane and articular cartilage in patients with osteoarthritis. The related factors in joint fluid have also been reported, but the expression of related factors in different stages of osteoarthritis is little reported. There are few reports on the correlation between these factors and the disease severity.
OBJECTIVE: To detect the expression of extracellular regulated protein kinase, matrix metalloproteinase 13 and a disintegrin and metalloproteinase with thrombospondin-like motifs 4/5 in patients with different stages of osteoarthritis.
METHODS: Ninety-four patients with osteoarthritis undergoing arthroscopic surgery at the Department of Orthopedics, Department of Orthopedics, the First Affiliated Hospital of the Medical College, Shihezi University, from October 2016 to December 2017 were included. According to clinical symptoms and K-L X-ray classification, the patients were divided into early- (n=27), medium- (n=32), and late-stage (n=35) groups. Ten healthy patients who underwent amputation, knee trauma undergoing arthroscopy examination and outpatients who volunteered to participate in the experiment were as control group. The synovial fluids of each group were collected to detect the expression levels of extracellular regulated protein kinase, matrix metalloproteinase 13 and a disintegrin and metalloproteinase with thrombospondin-like motifs 4/5 by qRT-PCR and ELISA. The study was approved by the Ethics Committee of the First Affiliated Hospital of the Medical College, Shihezi University, approval number: 2017-052-01.
RESULTS AND CONCLUSION: (1) The mRNA expression levels of each gene detected by qRT-PCR in the early-, middle- and late-stage groups were significantly higher than those in the control group (P < 0.001). The mRNA expression of extracellular regulated protein kinase and matrix metalloproteinase 13 in the early-, middle- and late-stage groups was on a rise (P < 0.01). The mRNA expression of a disintegrin and metalloproteinase with thrombospondin-like motifs 4/5 in the early-stage group was significantly higher than that in the middle- and late- stage groups (P < 0.01). (2) The protein expression levels of each gene detected by ELISA in the early-, middle- and late-stage groups were significantly higher than those in the control group (P < 0.001). The protein expression of extracellular regulated protein kinase and matrix metalloproteinase 13 in the early-, middle- and late-stage groups was on a rise (P < 0.01). The protein expression of a disintegrin and metalloproteinase with thrombospondin-like motifs 4/5 in the early-stage group was significantly higher than that in the middle- and late- stage groups (P < 0.01). (3) Correlation analysis showed that there was a positive correlation between extracellular regulated protein kinase and matrix metalloproteinase 13 expression (P < 0.01), a disintegrin and metalloproteinase with thrombospondin-like motifs 4 and 5 expression levels were positively correlated (P < 0.01). The expression levels of a disintegrin and metalloproteinase with thrombospondin-like motifs 4/5 were negatively correlated with the expression levels of extracellular regulated protein kinase and matrix metalloproteinase 13 (P < 0.05). (4) These results show that the expressions of extracellular regulated protein kinase, matrix metalloproteinase 13 and a disintegrin and metalloproteinase with thrombospondin-like motifs 4/5 are closely related to the clinical symptoms of knee osteoarthritis. The molecular mechanism of these factors in different stages of osteoarthritis is expected to provide reference for the clinical diagnosis and prognosis. 

Key words: osteoarthritis, joint fluids, extracellular regulated protein kinase, matrix metalloproteinase, a disintegrin and metalloproteinase with thrombospondin-like motifs, ADAMTS4/5

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