Insights into osteoarthritis development from single-cell RNA sequencing of subchondral bone

Shen, Ping; Löhning, Max

doi:10.1136/rmdopen-2022-002617

Cited by 4 publications

(2 citation statements)

References 47 publications

(48 reference statements)

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“…Presently, research primarily focuses on cartilage degeneration as a central aspect of OA’s pathogenesis, yet the underlying causes remain obscure. Clinical and basic research on cartilage remains pivotal in OA prevention and treatment ( 8 , 9 ). However, the acquisition of research specimens and the associated costs are considerable challenges.…”

Section: Introductionmentioning

confidence: 99%

The causal effect of cytokine cycling levels on osteoarthritis: a bidirectional Mendelian randomized study

Jiang,

Cai,

Yao

et al. 2024

Front. Immunol.

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ObjectiveOsteoarthritis (OA) is the most prevalent joint disease globally, serving as a primary cause of pain and disability. However, the pathological processes underlying OA remain incompletely understood. Several studies have noted an association between cytokines and OA, yet the causal link between them remains ambiguous. This study aims to identify cytokines potentially causally related to OA using Mendelian randomization (MR) analysis, informing early clinical diagnosis and treatment decisions.MethodsWe conducted a genome-wide association study (GWAS) on 12 OA traits involving 177,517 cases and 649,173 controls from 9 international cohorts. For discovery MR analysis, we used 103 cytokines from two European populations as instrumental variables (IVs). Concurrently, another European population OA GWAS database (36,185 cases and 135,185 controls) was used to replicate MR analysis, employing the inverse variance weighted (IVW) method as the primary analytic approach. Additional methods tested included MR Egger, Weighted median, and Weighted mode. We merged the MR findings through meta-analysis. Heterogeneity testing, level pleiotropy testing (MR Egger intercept test and MRPRESSO), and sensitivity analysis via Leave One Out (LOO) were conducted to verify result robustness. Lastly, reverse MR analysis was performed.ResultsThe meta-analysis merger revealed a correlation between CX3CL1 cycle levels and increased OA risk (OR=1.070, 95% CI: 1.040-1.110; P<0.010). We also observed associations between MCP4 (OR=0.930, 95% CI: 0.890-0.970; P<0.010) and CCL25 (OR=0.930, 95% CI: 0.890-0.970; P<0.010) with reduced OA risk. The sensitivity analysis results corroborate the robustness of these findings.ConclusionOur MR analysis indicates a potential causal relationship between CX3CL1, MCP4, CCL25, and OA risk changes. Further research is warranted to explore the influence of cytokines on OA development.

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Section: Introductionmentioning

confidence: 99%

The causal effect of cytokine cycling levels on osteoarthritis: a bidirectional Mendelian randomized study

Jiang,

Cai,

Yao

et al. 2024

Front. Immunol.

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“…At present, the pathogenesis of OA is not clear, but it is known that factors such as obesity, trauma, and lifestyle are all risk factors for the onset of OA [7][8][9], but even if these risk factors are avoided, the incidence rate of OA is still high. Preventing cartilage degeneration remains the key to preventing and treating OA [10,11]. However, there are currently no reliable biochemical biomarkers that can prevent the occurrence of OA [12,13].…”

Section: Introductionmentioning

confidence: 99%

The causal impact of bioavailable testosterone levels on osteoarthritis: a bidirectional Mendelian randomized study Running Title: Causality of testosterone on OA in bidirectional MR study

Jiang,

Yao,

Yang

et al. 2024

Preprint

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Background: It has been shown that low testosterone levels are associated with the development of osteoarthritis (OA). In our study, we aimed to investigate a bidirectional causal relationship between bioavailable testosterone levels and OA using Mendelian randomization (MR) analysis. Methods: In our study, the datasets from publicly available genome-wide association study (GWAS) were adopted, including the OA-related dataset (ukb-b-14486) and the bioavailable testosterone levels-related dataset (ebi-a-GCST90012104). In total, five methods were utilized, namely MR Egger, Weighted median, Inverse variance weighted (IVW), Simple mode, and Weighted mode. Among them, IVW was the main analytical method. Additionally, the sensitivity analysis was carried out through the heterogeneity test, the horizontal pleiotropy test, and the Leave-One-Out (LOO) method. Results: The result of forward MR analysis demonstrated that bioavailable testosterone levels were considerably relevant to OA, and were a risk factor for OA (OR = 1.009, 95% CI: 1.001-1.017, P = 0.020). However, through reverse MR analysis, we did not find a causal relationship between OA and bioavailable testosterone levels. Moreover, the results of the sensitivity analysis suggested that our results were reliable. Conclusion: The results of our study supported a causal relationship between bioavailable testosterone levels and OA.

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Bone/cartilage organoid on-chip: Construction strategy and application

Yan

Zhang

Wang

et al. 2023

Bioactive Materials

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Insights into osteoarthritis development from single-cell RNA sequencing of subchondral bone

Cited by 4 publications

References 47 publications

The causal effect of cytokine cycling levels on osteoarthritis: a bidirectional Mendelian randomized study

The causal effect of cytokine cycling levels on osteoarthritis: a bidirectional Mendelian randomized study

The causal impact of bioavailable testosterone levels on osteoarthritis: a bidirectional Mendelian randomized study Running Title: Causality of testosterone on OA in bidirectional MR study

Bone/cartilage organoid on-chip: Construction strategy and application

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