Mechanism underlying microRNA-214 regulation of cartilage and subchondral bone metabolism in osteoarthritis
- VernacularTitle:MicroRNA-214调控骨关节炎软骨和软骨下骨代谢的机制
- Author:
Sheng TIAN
1
;
Xi WANG
;
Yongcheng WANG
;
Yaning LIU
;
Hongquan YANG
Author Information
- Publication Type:Journal Article
- Keywords: microRNA-214; osteoarthritis; articular cartilage; tumor necrosis factor-α; interleukin-6; subchondral bone
- From: Chinese Journal of Tissue Engineering Research 2025;29(12):2466-2474
- CountryChina
- Language:Chinese
- 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.
