Chinese Journal of Tissue Engineering Research ›› 2025, Vol. 29 ›› Issue (12): 2466-2474.doi: 10.12307/2025.389

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Mechanism underlying microRNA-214 regulation of cartilage and subchondral bone metabolism in osteoarthritis

Tian Sheng1, Wang Xi2, 3, Wang Yongcheng4, Liu Yaning3, Yang Hongquan1   

  1. 1Graduate School of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou 014000, Inner Mongolia Autonomous Region, China; 2Guang’an District People’s Hospital of Guang’an City, Guang’an 638000, Sichuan Province, China; 3Inner Mongolia Medical University, Hohhot 010000, Inner Mongolia Autonomous Region, China; 4Orthopedic Center, Inner Mongolia People’s Hospital, Hohhot 010000, Inner Mongolia Autonomous Region, China
  • Received:2024-03-19 Accepted:2024-06-07 Online:2025-04-28 Published:2024-09-09
  • Contact: Wang Yongcheng, MD, Chief physician, Master’s supervisor, Orthopedic Center, Inner Mongolia People’s Hospital, Hohhot 010000, Inner Mongolia Autonomous Region, China
  • About author:Tian Sheng, Master candidate, Graduate School of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou 014000, Inner Mongolia Autonomous Region, China
  • Supported by:
     Inner Mongolia Natural Science Foundation, No. 2020MS08054 (to WYC); Joint Project of Inner Mongolia Medical University, No. YKD2021LH037 (to WYC); 2022 Autonomous Region Health and Wellness Science and Technology Program Project, No. 202201013 (to WYC)

Abstract: BACKGROUND: The role of microRNA-214 in osteoporosis has been reported both at home and abroad, whereas the interrelationship between microRNA-214 and osteoarthritic articular cartilage and subchondral bone degeneration is unclear. 
OBJECTIVE: To investigate the relationship between microRNA-214 and cartilage and subchondral bone degeneration in mice with knee osteoarthritis. 
METHODS: Thirty C57BL/6J mice were randomly grouped: Experiment 1: sham operation group and medial meniscus destabilization group (n=3 per group) underwent hematoxylin-eosin staining and qPCR to detect changes in microRNA-214 gene expression; Experiment 2: sham operation group, medial meniscus destabilization group, medial meniscus destabilization+null-loaded adenovirus group (null-loaded group), and medial meniscus destabilization+microRNA-214 antagonist overexpression adenovirus group (antagonist group; n=6 per group). Cartilage tissues were taken from each group 4 weeks after surgery, and stained with hematoxylin-eosin, safranin O-fast green, and toluidine blue. qPCR and western blot were used to detect the expression of related factors in articular cartilage.
RESULTS AND CONCLUSION: (1) In Experiment 1, hematoxylin-eosin staining results showed that cartilage degeneration was visible in the medial meniscus destabilization group compared with the sham operation group. qPCR assay results showed that microRNA-214 was expressed in all the samples, and the expression level of microRNA-214 in cartilage samples of the medial meniscus destabilization group was significantly higher than that of the sham operation group (P < 0.05). (2) In Experiment 2, the results of hematoxylin-eosin staining, safranin O-fast green staining, and toluidine blue staining showed that the degree of cartilage degeneration in the antagonist group was significantly reduced compared with the medial meniscus destabilization group. Adenovirus-validated PCR assay showed that the microRNA-214 expression level in cartilage tissue was higher in the null-loaded group than in the antagonist group (P < 0.05). (3) In Experiment 2, X-ray results showed typical osteoarthritis imaging changes in the medial meniscus destabilization group and null-loaded group, while the degree of degenerative joint lesions was relatively mild in the antagonist group. The results of microcomputed tomography showed that after injection of microRNA-214 antagonist, trabecular structure model index became smaller in the antagonist group, and the data were better than those of the medial meniscus destabilization group and null-loaded group. (4) In Experiment 2, western blot results showed that The relative expression levels of cartilage-associated factor type II collagen α1, sex-determining region Y-box 9, Runt-associated transcription factor 2, and osteopontin in cartilage specimens of the medial meniscus destabilization group and the null-loaded group were lower than that in the sham operation group and the antagonist group (P < 0.05), whereas the relative expression level of matrix metalloproteinase 13 was higher in the medial meniscus destabilization group and the null-loaded group than the sham operation group and the antagonist group (P < 0.05). (5) In Experiment 2, PCR results indicated that the relative mRNA expression of tumor necrosis factor-α and interleukin-6 was relatively higher in the medial meniscus destabilization group and null-loaded group, but relatively lower in the antagonist group, as compared with the sham operation group (P < 0.05). The relative mRNA expression of tumor necrosis factor-α and interleukin-6 was also higher in the medial meniscus destabilization group and the null-loaded group compared with the antagonist group (P < 0.05). To conclude, the expression level of microRNA-214 in articular cartilage was elevated in the mouse osteoarthritis model, suggesting that the elevated expression level of microRNA-214 is closely related to osteoarthritis; and injection of microRNA-214 antagonist into the knee joint cavity of the mouse osteoarthritis model could delay articular cartilage degradation, promote subchondral bone remodeling, and ameliorate the progression of osteoarthritis.

中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程

Key words: microRNA-214, osteoarthritis, articular cartilage, tumor necrosis factor-α, interleukin-6, subchondral bone

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