Objective. Osteoarthritis (OA) is a complex arthritic condition in which the genetic factor plays a major role. One of the candidate genes of is the ADAM12 gene, but no consistency has been reached till now. This study aims to investigate the potential role of four single nucleotide polymorphisms (SNPs) of the ADAM12 gene in susceptibility to knee OA and its progression in Chinese Han population. Methods. The rs1278279, rs3740199, rs1044122, and rs1871054 polymorphisms were genotyped and compared in a population based cohort consisting of 164 OA subjects and 200 age- and gender-matched controls. Results. The SNP rs1871054 was found with increased risk of OA susceptibility in comparing the genotype frequencies between the case and control groups no matter for which model of comparison (allele level, dominant model, recessive model, and extreme genotype model). Additionally, the SNP rs1871054 was found associated with increased OA severity according to the K/L grade. Conclusion. In summary, we have identified that the rs1871054 variant within the ADAM12 gene is a risk factor for increased osteoarthritis susceptibility and severity.

Inflammation of cartilage is a primary symptom for knee-joint osteoarthritis. Matrix metalloproteinases (MMPs) are known to play an important role in the articular cartilage destruction related to osteoarthritis. Naringenin is a plant-derived flavonoid known for its anti-inflammatory properties. We studied the effect of naringenin on the transcriptional expression, secretion and enzymatic activity of MMP-3 in vivo in the murine monosodium iodoacetate (MIA) osteoarthritis model. The assessment of pain behavior was also performed in the MIA rats. The destruction of knee-joint tissues was analyzed microscopically. Moreover, the effect of naringenin was also studied in vitro in IL-1β activated articular chondrocytes. The transcriptional expression of MMP-3, MMP-1, MMP-13, thrombospondin motifs (ADAMTS-4) and ADAMTS-5 was also studied in primary cultured chondrocytes of rats. Naringenin caused significant reduction in pain behavior and showed marked improvement in the tissue morphology of MIA rats. Moreover, a significant inhibition of MMP-3 expression in MIA rats was observed upon treatment with naringenin. In the in vitro tests, naringenin caused a significant reduction in the transcriptional expression, secretion and enzymatic activity of the studied degradative enzymes. The NF-κB pathway was also found to be inhibited upon treatment with naringenin in vitro. Overall, the study suggests that naringenin alleviated pain and regulated the production of matrix-metalloproteinases via regulation of NF-κB pathway. Thus, naringenin could be a potent therapeutic option for the treatment of osteoarthritis.

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BackgroundRheumatoid arthritis (RA) is a chronic auto-inflammatory disorder of joints. The present study aimed to identify the key genes in RA for better understanding the underlying mechanisms of RA.MethodsThe integrated analysis of expression profiling was conducted to identify differentially expressed genes (DEGs) in RA. Moreover, functional annotation, protein–protein interaction (PPI) network and transcription factor (TF) regulatory network construction were applied for exploring the potential biological roles of DEGs in RA. In addition, the expression level of identified candidate DEGs was preliminarily detected in peripheral blood cells of RA patients in the dataset. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to validate the expression levels of identified DEGs in RA.ResultsA total of 378 DEGs, including 202 up- and 176 down-regulated genes, were identified in synovial tissues of RA patients compared with healthy controls. DEGs were significantly enriched in axon guidance, RNA transport and MAPK signaling pathway. RBFOX2, LCK and SERBP1 were the hub proteins in the PPI network. In the TF-target gene network, RBFOX2, POU6F1, WIPF1 and PFKFB3 had the high connectivity with TFs. The expression status of 11 candidate DEGs was detected in , the expression levels of MAT2A and NSA2 were significantly down-regulated and CD47 had the up-regulated tendency in peripheral blood cells of patients with RA compared with healthy individuals. qRT-PCR results of MAT2A, NSA2, CD47 were compatible with our bioinformatics analyses.DiscussionOur study might provide valuable information for exploring the pathogenesis mechanism of RA and identifying the potential biomarkers for RA diagnosis.

The present study aimed to explore genetic association of receptor activator nuclear factor κB (RANK) polymorphisms with individual susceptibility to knee osteoarthritis (OA) in different Kellgren–Lawrence (KL) grades. This case–control study included 138 knee OA patients and 145 healthy individuals. RANK rs1805034 and rs8086340 polymorphisms were genotyped through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The effects of RANK polymorphisms on knee OA risk were analyzed via χ 2 test or Fisher exact test, and the results were expressed using odds ratios (ORs) with corresponding 95% confidence intervals (CIs). The C allele of rs1805034 polymorphism had significantly higher frequency in knee OA patients than in controls ( P = .044), indicating that this allele could increase the risk of knee OA (OR = 1.424, 95% CI = 1.010–2.008). Besides, the CC genotype and C allele of the rs1805034 polymorphism were significantly associated with elevated risk of knee OA in moderate grade (CC vs TT: P = .018, OR = 3.071, 95% CI = 1.187–7.941; C vs T: P = .012, OR = 1.787, 95% CI = 1.131–2.823). However, rs8086340 polymorphism had no significant association with knee OA risk The C allele of RANK rs1805034 polymorphism is closely correlated with increased risk of knee OA, especially for moderate grade.