Association of thyroid hormone with osteoarthritis: from mendelian randomization and RNA sequencing analysis.
Diagnosis value
Hypertrophic chondrocyte
Mendelian randomization
Osteoarthritis
Thyroid hormone levels
Triiodothyronine targeted genes
Journal
Journal of orthopaedic surgery and research
ISSN: 1749-799X
Titre abrégé: J Orthop Surg Res
Pays: England
ID NLM: 101265112
Informations de publication
Date de publication:
25 Jul 2024
25 Jul 2024
Historique:
received:
11
06
2024
accepted:
21
07
2024
medline:
26
7
2024
pubmed:
26
7
2024
entrez:
25
7
2024
Statut:
epublish
Résumé
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. 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). 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. 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.
Sections du résumé
BACKGROUND
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
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
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
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.
Identifiants
pubmed: 39054551
doi: 10.1186/s13018-024-04939-x
pii: 10.1186/s13018-024-04939-x
doi:
Substances chimiques
Triiodothyronine
06LU7C9H1V
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
429Subventions
Organisme : National Natural Science Foundation of China
ID : 82201719
Organisme : National Natural Science Foundation of China
ID : 82201719
Organisme : National Natural Science Foundation of China
ID : 82201719
Organisme : National Natural Science Foundation of China
ID : 82201719
Organisme : National Natural Science Foundation of China
ID : 82201719
Organisme : National Natural Science Foundation of China
ID : 82201719
Organisme : National Natural Science Foundation of China
ID : 82201719
Organisme : National Natural Science Foundation of China
ID : 82201719
Organisme : National Natural Science Foundation of China
ID : 82201719
Organisme : National Natural Science Foundation of China
ID : 82201719
Organisme : National Natural Science Foundation of China
ID : 82201719
Organisme : National Natural Science Foundation of China
ID : 82201719
Organisme : National Natural Science Foundation of China
ID : 82201719
Organisme : National Natural Science Foundation of China
ID : 82201719
Informations de copyright
© 2024. The Author(s).
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