Are functional variants of the microRNA-146a gene associated with primary knee OA? Evidence in Mexican mestizo population

Miranda‐Duarte, Antonio; Borgonio-Cuadra, Verónica Marusa; González-Huerta, Norma Celia; Rojas-Toledo, Emma Xochitl; Ahumada-Pérez, Juan Francisco; Morales-Hernández, Eugenio; Pérez-Hernández, Nonanzit; Rodríguez-Pérez, José Manuel; Vargas‐Alarcón, Gilberto

doi:10.1007/s11033-021-06207-1

Cited by 3 publications

(10 citation statements)

References 49 publications

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“…The following studies were excluded due to: study not report the specific results or results could not be extracted (12); lack of nonOA health control (6); basic research (6); study compare OA and RA population (4); study not related to mir-146a (3); study only report the changes of miR-146a expression before and after OA treatment (3); review (1). Finally, 26 articles were included in the analysis [ 16 – 41 ]. The selection process of eligible study was detailed in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) flow diagram (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The included studies were published from 2010 to 2021 and included two large-scale SNP-related studies [ 16 , 24 ] and two reported diagnostic accuracy results [ 18 , 27 ]. The tissue source for the miR-146a test included plasma, regulatory T cells, peripheral blood mononuclear cells (PBMCs), local synovial fluid, synovial tissue, synoviocytes, cartilage tissue, and chondrocytes.…”

Section: Resultsmentioning

confidence: 99%

“…Two studies focused on SNPs of miR-146a [ 16 , 24 ]. For the rs2910164 locus, there were no significant results in any model [allele model (OR: 1.09; 95% CI 0.95, 1.24; p = 0.205); heterozygous model (OR: 1.14; 95% CI 0.96, 1.35; p = 0.125); homozygous model (OR: 1.08; 95% CI 0.75,1.56; p = 0.690); dominant model (OR: 1.13; 95% CI 0.96, 1.34; p = 1.32); recessive model (OR: 1.03; 95% CI 0.72, 1.47; p = 0.879)].…”

Section: Resultsmentioning

confidence: 99%

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MiR-146a expression profiles in osteoarthritis in different tissue sources: a meta-analysis of observational studies

Liu

Liang

2022

J Orthop Surg Res

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Background MiR-146a has been widely studied in the pathogenesis of osteoarthritis (OA); however, the results are still controversial. Objective This meta-analysis analyzes the expression profile of miR-146a in various tissues of OA patients. Methods Public databases were searched for appropriate studies published up to September 1, 2021. A case–control study comparing the OA population and a non-OA healthy population was included. Results 26 articles were included in analysis. The results showed that the expression level of miR-146a in peripheral blood mononuclear cells (PBMCs) was significantly higher in OA patients than in controls (SMD: 1.23; 95% CI 0.08–2.37; p = 0.035) but not in plasma (SMD: 1.09; 95% CI − 0.06, 2.24; p = 0.064). The expression level of miR-146a in cartilage was also significantly higher in OA patients than in controls (SMD: 6.39; 95% CI 0.36, 12.4; p = 0.038) but not in chondrocytes (SMD: − 0.71; 95% CI − 4.15, 2.73; p = 0.687). The miR-146a level was significantly lower in synoviocytes in the OA population than in control patients (SMD: − 0.97; 95% CI − 1.68, − 0.26; p = 0.008). In synovial tissue, synovial fluid, and regulatory T cells, there was no significant difference. Conclusion The expression level of miR-146a in cartilage tissue and PBMCs was significantly higher in OA patients than in non-OA healthy controls. Due to the limitations of this study, more research is needed to confirm these results in the future. Trial registration: retrospectively registered.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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MiR-146a expression profiles in osteoarthritis in different tissue sources: a meta-analysis of observational studies

Liu

Liang

2022

J Orthop Surg Res

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“…To date, two large-scale SNP-related studies (focused on SNPs of miR-146a) 17,18 investigated the association of the miR-146a SNP rs2910164 (G>C) with a predisposition to PKOA. The first one, published in 2020, 17 evaluated the association between miR-146a rs2910164 (G>C) gene polymorphism and POA risk in a case-control study of 1688 participants (950 PKOA patients and 738 healthy individuals) of Greek origin.…”

Section: Discussionmentioning

confidence: 99%

“…That led to the investigation of the association of the miR-146a SNP rs2910164 (G>C) with a predisposition to primary knee osteoarthritis (PKOA) in different populations (Greek, Mexican) without evidence of susceptibility to PKOA. 17,18 In a recently published article, Stefik et al 19 investigated 10 different SNPs in Toll-like receptors (TLRs) genes (TLR2, TLR3, TLR4, TLR7, TLR9), and miRNA genes that regulate TLR signaling (miR-146a, miR-155, and miR-196a2) and their association with advanced stage POA risk in 61 primary hip osteoarthritis (PHOA) patients and 34 PKOA patients. Although it was the first study that investigated the association of the miR-146a SNP rs2910164 with a predisposition to PHOA, the authors have not found the association of this SNP with PHOA susceptibility.…”

Section: Introductionmentioning

confidence: 99%

Indirect influence of microRNA‐146a on the association of IL‐6 and TNF‐α genetic polymorphisms with the increased risk of hip osteoarthritis

Tudor,

Baranasic,

Knezevic

et al. 2024

Journal Orthopaedic Research

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Primary osteoarthritis (POA) is a complex hereditary disease that involves the interplay between genetics and epigenetics. MicroRNA molecules play important roles in epigenetic mechanisms. MicroRNA‐146a (miR‐146a) is a negative regulator of the immune response in osteoarthritis (OA). So, variations in the miR‐146a gene could affect OA risk. The aim of this study was to investigate the relationships between single nucleotide polymorphisms (SNPs) in the miR‐146a, interleukin‐6 (IL‐6), Toll‐like receptor 10 (TLR10), and tumor necrosis factor‐alpha (TNFA) genes and the risk for development of advanced‐stage primary hip osteoarthritis (PHOA) and primary knee osteoarthritis (PKOA) in the Croatian population. A total of 609 POA patients and 656 healthy donors were genotyped for SNPs in the miR‐146a (rs2910164, G>C). Since we used same patients and controls as two studies before us, we already had information about IL‐6 (rs1800795, C>G), TLR10 (rs11096957, C>T), and TNFA (rs1800629, C>T) genotypes of our subjects. None of the differences were statistically significant comparing either allelic or genotypic frequencies of miR‐146a SNP rs2910164 (G>C) between the PHOA and PKOA patients and controls. However, we found a significant association with risk to PHOA for the combination of genotypes (stratified miR‐146a genotype with the IL‐6, and stratified miR‐146a genotype with the TNFA). In a multifactorial disease such as POA, we have shown the indirect relevance of a second modifying factor (miR‐146a), which apparently contributes to the overall risk of PHOA. There was no risk association with the PKOA, indicating that these two localities (hip and knee) might have different risk‐modifying factors.

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Exosomes derived from miR-146a-overexpressing fibroblast-like synoviocytes in cartilage degradation and macrophage M1 polarization: a novel protective agent for osteoarthritis?

Wang,

Zhang,

Zhang

et al. 2024

Front. Immunol.

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IntroductionPathological changes in the articular cartilage (AC) and synovium are major manifestations of osteoarthritis (OA) and are strongly associated with pain and functional limitations. Exosome-derived microRNAs (miRNAs) are crucial regulatory factors in intercellular communication and can influence the progression of OA by participating in the degradation of chondrocytes and the phenotypic transformation in the polarization of synovial macrophages. However, the specific relationships and pathways of action of exosomal miRNAs in the pathological progression of OA in both cartilage and synovium remain unclear.MethodsThis study evaluates the effects of fibroblast-like synoviocyte (FLS)-derived exosomes (FLS-Exos), influenced by miR-146a, on AC degradation and synovial macrophage polarization. We investigated the targeted relationship between miR-146a and TRAF6, both in vivo and in vitro, along with the involvement of the NF-κB signaling pathway.ResultsThe expression of miR-146a in the synovial exosomes of OA rats was significantly higher than in healthy rats. In vitro, the upregulation of miR-146a reduced chondrocyte apoptosis, whereas its downregulation had the opposite effect. In vivo, exosomes derived from miR-146a-overexpressing FLSs (miR-146a-FLS-Exos) reduced AC injury and chondrocyte apoptosis in OA. Furthermore, synovial proliferation was reduced, and the polarization of synovial macrophages shifted from M1 to M2. Mechanistically, the expression of TRAF6 was inhibited by targeting miR-146a, thereby modulating the Toll-like receptor 4/TRAF6/NF-κB pathway in the innate immune response.DiscussionThese findings suggest that miR-146a, mediated through FLS-Exos, may alleviate OA progression by modulating cartilage degradation and macrophage polarization, implicating the NF-κB pathway in the innate immune response. These insights highlight the therapeutic potential of miR-146a as a protective agent in OA, underscoring the importance of exosomal miRNAs in the pathogenesis and potential treatment of the disease.

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Are functional variants of the microRNA-146a gene associated with primary knee OA? Evidence in Mexican mestizo population

Cited by 3 publications

References 49 publications

MiR-146a expression profiles in osteoarthritis in different tissue sources: a meta-analysis of observational studies

MiR-146a expression profiles in osteoarthritis in different tissue sources: a meta-analysis of observational studies

Indirect influence of microRNA‐146a on the association of IL‐6 and TNF‐α genetic polymorphisms with the increased risk of hip osteoarthritis

Exosomes derived from miR-146a-overexpressing fibroblast-like synoviocytes in cartilage degradation and macrophage M1 polarization: a novel protective agent for osteoarthritis?

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