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已发表论文
长链非编码 RNA NONHSAT248596.1 通过 miR-146a-5p/CXCR4 轴诱导软骨细胞凋亡和细胞外基质降解从而促进骨关节炎
Authors Yang X, Yang G, Yang T, Song E, Xiang Y, Shi Z, Yu Y, Wang G, Li Y
Received 6 August 2025
Accepted for publication 3 December 2025
Published 10 December 2025 Volume 2025:18 Pages 17235—17252
DOI https://doi.org/10.2147/JIR.S558704
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Ujjwol Risal
Xianguang Yang,1 Guang Yang,2 Tengyun Yang,3 En Song,1 Yaoyu Xiang,1 Zhengliang Shi,1 Yue Yu,1 Guoliang Wang,1 Yanlin Li1
1Department of Sports Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 2Department of Joint and Sports Medicine, The First People’s Hospital of Qujing City, Qujing, Yunnan, People’s Republic of China; 3Orthopedic Department, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China
Correspondence: Yanlin Li, Department of Sports Medicine, The First Affiliated Hospital of Kunming Medical University, No. 295 Xichang Road, Kunming, Yunnan, 650032, People’s Republic of China, Email liyanlin@kmmu.edu.cn Guoliang Wang, Department of Sports Medicine, The First Affiliated Hospital of Kunming Medical University, No. 295 Xichang Road, Kunming, Yunnan, 650032, People’s Republic of China, Email 200301144@163.com
Objective: Osteoarthritis (OA) is characterized by articular cartilage degeneration, osteophyte formation, subchondral bone remodeling, synovitis, and joint capsule fibrosis, yet its underlying molecular mechanisms and the functional roles of long non-coding RNAs (lncRNAs) remain poorly understood. This study aimed to investigate the role of lncRNA NONHSAT248596.1 in the pathogenesis of OA through the miR-146a-5p/CXCR4 axis.
Materials and Methods: The experimental systems included human articular cartilage samples, a rabbit model of OA, and chondrocytes treated with 100 ng/mL SDF-1. DIANA software predicted lncRNAs targeting the miR-146a-5p/CXCR4 axis. Dual-luciferase reporter assay verified the molecular interactions. The expression levels of target genes and proteins (CXCR4, miR-146a-5p, NONHSAT248596.1, TNF-α, IL-1β, MMP-13, collagen II, and aggrecan) were analyzed using qRT-PCR, Western blotting, and ELISA both in vitro and in vivo. Cell viability and apoptosis were measured by CCK-8 assay and flow cytometry, respectively. Cartilage pathology in the rabbit models was assessed via safranin O and hematoxylin and eosin staining at 4, 8, and 12 weeks.
Results: LncRNA NONHSAT248596.1 was significantly upregulated in OA patients and in SDF-1-induced chondrocytes. The dual-luciferase assays confirmed that NONHSAT248596.1 interacted with miR-146a-5p, and miR-146a-5p interacted with CXCR4 in OA. Overexpression of NONHSAT248596.1 promoted chondrocyte apoptosis (p< 0.0001, n=3), upregulated MMP-13 (p< 0.0001, n=3), and downregulated collagen II (p< 0.0001, n=3) and aggrecan (p< 0.01, n=3), while exacerbating cartilage degradation (p< 0.05, n=3/group/time point). Silencing NONHSAT248596.1 or overexpressing miR-146a-5p reduced chondrocyte apoptosis and extracellular matrix degradation in vitro, which also ameliorated cartilage degradation (Mankin score: 5.9± 1.7 VS 2.4± 0.59, p< 0.0001, n=3/group/time point) in rabbit OA models.
Conclusion: LncRNA NONHSAT248596.1 promotes OA via miR-146a-5p/CXCR4 axis by inducing chondrocyte apoptosis and extracellular matrix degradation. These results identify NONHSAT248596.1 as a potential therapeutic target for OA intervention and underscore the miR-146a-5p/CXCR4 axis as a critical regulatory pathway for cartilage protection.
Keywords: osteoarthritis, competing endogenous RNA, lncRNA NONHSAT248596.1, CXCR4, miR-146a-5p, chondrocyte apoptosis, extracellular matrix degradation
1Department of Sports Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 2Department of Joint and Sports Medicine, The First People’s Hospital of Qujing City, Qujing, Yunnan, People’s Republic of China; 3Orthopedic Department, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China
Correspondence: Yanlin Li, Department of Sports Medicine, The First Affiliated Hospital of Kunming Medical University, No. 295 Xichang Road, Kunming, Yunnan, 650032, People’s Republic of China, Email liyanlin@kmmu.edu.cn Guoliang Wang, Department of Sports Medicine, The First Affiliated Hospital of Kunming Medical University, No. 295 Xichang Road, Kunming, Yunnan, 650032, People’s Republic of China, Email 200301144@163.com
Objective: Osteoarthritis (OA) is characterized by articular cartilage degeneration, osteophyte formation, subchondral bone remodeling, synovitis, and joint capsule fibrosis, yet its underlying molecular mechanisms and the functional roles of long non-coding RNAs (lncRNAs) remain poorly understood. This study aimed to investigate the role of lncRNA NONHSAT248596.1 in the pathogenesis of OA through the miR-146a-5p/CXCR4 axis.
Materials and Methods: The experimental systems included human articular cartilage samples, a rabbit model of OA, and chondrocytes treated with 100 ng/mL SDF-1. DIANA software predicted lncRNAs targeting the miR-146a-5p/CXCR4 axis. Dual-luciferase reporter assay verified the molecular interactions. The expression levels of target genes and proteins (CXCR4, miR-146a-5p, NONHSAT248596.1, TNF-α, IL-1β, MMP-13, collagen II, and aggrecan) were analyzed using qRT-PCR, Western blotting, and ELISA both in vitro and in vivo. Cell viability and apoptosis were measured by CCK-8 assay and flow cytometry, respectively. Cartilage pathology in the rabbit models was assessed via safranin O and hematoxylin and eosin staining at 4, 8, and 12 weeks.
Results: LncRNA NONHSAT248596.1 was significantly upregulated in OA patients and in SDF-1-induced chondrocytes. The dual-luciferase assays confirmed that NONHSAT248596.1 interacted with miR-146a-5p, and miR-146a-5p interacted with CXCR4 in OA. Overexpression of NONHSAT248596.1 promoted chondrocyte apoptosis (p< 0.0001, n=3), upregulated MMP-13 (p< 0.0001, n=3), and downregulated collagen II (p< 0.0001, n=3) and aggrecan (p< 0.01, n=3), while exacerbating cartilage degradation (p< 0.05, n=3/group/time point). Silencing NONHSAT248596.1 or overexpressing miR-146a-5p reduced chondrocyte apoptosis and extracellular matrix degradation in vitro, which also ameliorated cartilage degradation (Mankin score: 5.9± 1.7 VS 2.4± 0.59, p< 0.0001, n=3/group/time point) in rabbit OA models.
Conclusion: LncRNA NONHSAT248596.1 promotes OA via miR-146a-5p/CXCR4 axis by inducing chondrocyte apoptosis and extracellular matrix degradation. These results identify NONHSAT248596.1 as a potential therapeutic target for OA intervention and underscore the miR-146a-5p/CXCR4 axis as a critical regulatory pathway for cartilage protection.
Keywords: osteoarthritis, competing endogenous RNA, lncRNA NONHSAT248596.1, CXCR4, miR-146a-5p, chondrocyte apoptosis, extracellular matrix degradation