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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. [ABSTRACT FROM AUTHOR]

Background: Bone marrow mesenchymal stem cells (BMMSCs) are commonly used for cell transplantation to treat refractory diseases. However, the presence of inflammatory factors, such as tumour necrosis factor-alpha (TNF-α), at the transplantation site severely compromises the stemness of BMMSCs, thereby reducing the therapeutic effect of cell transplantation. Aspirin (AS) is a drug that has been in use for over a century and has a wide range of effects, including the regulation of cell proliferation, multidirectional differentiation, and immunomodulatory properties of stem cells. However, it is still unclear whether AS can delay the damaging effects of TNF-α on BMMSC stemness., Methods: This study investigated the effects of AS and TNF-α on BMMSC stemness and the molecular mechanisms using colony formation assay, western blot, qRT-PCR, and overexpression or knockdown of YAP and SMAD7., Results: The results demonstrated that TNF-α inhibited cell proliferation, the expression of stemness, osteogenic and chondrogenic differentiation markers of BMMSCs. Treatment with AS was shown to mitigate the TNF-α-induced damage to BMMSC stemness. Mechanistic studies revealed that AS may reverse the damage caused by TNF-α on BMMSC stemness by upregulating YAP and inhibiting the expression of SMAD7., Conclusion: AS can attenuate the damaging effects of TNF-α on BMMSC stemness by regulating the YAP-SMAD7 axis. These findings are expected to promote the application of AS to improve the efficacy of stem cell therapy., (© 2024. The Author(s).)

Objectives: Numerous studies have established the role of inflammation in osteoarthritis (OA) progression, yet limited research explores the association between systemic inflammatory indicators and pre-diagnosis OA risk. This study aimed to investigate the association between peripheral inflammatory indicators and the risk of OA using data from the UK Biobank., Methods: The study analyzed data from 417,507 participants in the UK Biobank, including neutrophil count, lymphocyte count, monocyte count, platelet count, and C-reactive protein meter. Additionally, derived ratios such as NLR(neutrophils-lymphocytes ratio), PLR(Platelets-lymphocytes ratio), SII(systemic immune-inflammation index), and LMR (lymphocytes-monocytes ratio) were examined. Cox proportional hazards models and restricted cubic spline models were used to assess both linear and nonlinear associations., Results: Over a mean follow-up period of 12.7 years, a total of 49,509 OA events were identified. The findings revealed that CRP (HR:1.06, 95%CI:1.05-1.07), NLR (HR:1.02, 95%CI:1.01-1.03), PLR (HR:1.02, 95%CI:1.01-1.03), and SII (HR:1.03, 95%CI:1.01-1.04) were associated with an increased risk of OA, while LMR (HR:0.97, 95%CI:0.96-0.99) showed a significant negative correlation with OA risk. Subgroup analyses further emphasized that these associations were significant across most of the population. Although neutrophils, lymphocytes, monocytes, and platelets showed a nominal association with the risk of OA, the results were unreliable, especially for specific joint OA., Conclusion: The study provides evidence of a significant association between elevated peripheral inflammatory indicators and OA risk. These findings underscore the importance of low-grade chronic inflammation in OA development. The potential clinical utility of these indicators as early predictors of OA is suggested, warranting further exploration., Competing Interests: The authors declared that no competing interests exist., (© 2024 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International (OARSI).)