Association of thyroid hormone with osteoarthritis: from mendelian randomization and RNA sequencing analysis.

Autor: Li C; Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Zhong Shan 2nd Road, No. 58, Guangzhou, 510080, Guangdong, China., Tu Y; Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Zhong Shan 2nd Road, No. 58, Guangzhou, 510080, Guangdong, China., Rong R; Department of Nosocomial Infection, The First Affiliated Hospital, Sun Yat-Sen University, Zhong Shan 2nd Road, No. 58, Guangzhou, 510080, Guangdong, China., Zhang Z; Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Zhong Shan 2nd Road, No. 58, Guangzhou, 510080, Guangdong, China., Chen W; Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Zhong Shan 2nd Road, No. 58, Guangzhou, 510080, Guangdong, China., Long L; Research Center of Translational Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Zhong Shan 2nd Road, No. 58, Guangzhou, 510080, Guangdong, China., Zhang Y; Department of Orthopedics, People's Hospital of Shenzhen Baoan District, 118 Longjing 2nd Road, Shenzhen, 518101, Guangdong, China., Wang C; Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Zhong Shan 2nd Road, No. 58, Guangzhou, 510080, Guangdong, China., Pan B; Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Zhong Shan 2nd Road, No. 58, Guangzhou, 510080, Guangdong, China., Wu X; Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Zhong Shan 2nd Road, No. 58, Guangzhou, 510080, Guangdong, China., Guan M; Joint Surgery Center, Foshan Traditional Chinese Medicine Hospital, 6 Qinren Road, Foshan, 528200, Guangdong, China., Yang B; Department of Orthopedics, The First Affiliated Hospital of Shantou University Medical College, 57 Chenghai Road, Shantou, 515041, Guangdong, China., Zheng L; Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Zhong Shan 2nd Road, No. 58, Guangzhou, 510080, Guangdong, China. zhenglli3@mail.sysu.edu.cn., Sheng P; Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Zhong Shan 2nd Road, No. 58, Guangzhou, 510080, Guangdong, China. shengpy@mail.sysu.edu.cn.
Jazyk: angličtina
Zdroj: Journal of orthopaedic surgery and research [J Orthop Surg Res] 2024 Jul 25; Vol. 19 (1), pp. 429. Date of Electronic Publication: 2024 Jul 25.
DOI: 10.1186/s13018-024-04939-x
Abstrakt: Background: The relationship between thyroid hormone (TH) levels in vivo and osteoarthritis (OA) remains inconclusive. This study aims to investigate the association between TH levels and OA, analyze the effect of triiodothyronine on hypertrophic chondrocyte differentiation and OA progression, and identify potential target genes of triiodothyronine in OA to evaluate its diagnostic value.
Methods: Two-sample mendelian randomization method was used to probe the causal links between hyperthyroidism and OA. Differentially expressed genes (DEGs) from two RNA-sequencing data in Gene Expression Omnibus (GSE199847 and GSE114007) and enrichment analysis of DEGs (166 commonly upregulated genes and 71 commonly downregulated genes of GSE199847 and GSE114007) was performed to analyze the effect of triiodothyronine (T3) on hypertrophic chondrocyte differentiation and OA. C28/I2 cells treated with T3 and reverse transcription and quantitative real-time polymerase chain reaction were used to validate T3 targeted genes. The diagnostic performance of target genes was assessed by the receiver operating characteristic (ROC) curve and area under the curve (AUC).
Results: There was a positive causal association between hyperthyroidism and OA (IVW result, OR = 1.330, 95% CI 1.136-1.557, P = 0.0004). Weighted median and Weighted mode analysis also demonstrated that hyperthyroidism had a positive causal association with OA (p < 0.05, OR > 1). Bioinformatics analysis indicated T3 can partially induce the emergence of late hypertrophic chondrocyte and promote OA through extracellular matrix organization, blood vessel development, skeletal system development and ossification. Post-T3 treatment, MAFB, C1QTNF1, COL3A1 and ANGPTL2 were significantly elevated in C28/I2 cells. ROC curves in GSE114007 showed that AUC of all above genes were ≥ 0.7.
Conclusions: This study identified that hyperthyroidism has a positive causal association with OA by MR analysis. T3 induced hypertrophic chondrocytes promote OA progression by upregulating genes such as MAFB, C1QTNF1, COL3A1 and ANGPTL2, which can also serve as OA diagnosis.
(© 2024. The Author(s).)
Databáze: MEDLINE
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