Identification and Molecular Mechanisms Study of Genes Associated with Osteoarthritis: A Comprehensive Bioinformatic Study of Cartilage and Synovium.

Osteoarthritis (OA) is a severe disease and has brought a massive burden to people's daily life. This study was performed to explore the hub genes associated with OA and predict potential biomarkers for OA. The cartilage (GSE114007) and synovial (GSE55235 and GSE55457) datasets downloaded from the Gene Expression Omnibus (GEO) database were used to screen the differentially expressed genes in OA compared with normal tissues. Then, based on weighted gene co-expression network analysis, the intersection genes between cartilage and synovium data were screened. The protein-protein interaction network and receiver operating characteristic (ROC) curve analysis were utilized to identify the OA-related hub genes. The gene ontology (GO), kyoto encyclopedia of genes and genomes (KEGG), and gene set variation analysis (GSVA) databases were used to explore the potential molecular mechanism of genes. Single-sample gene set enrichment analysis was performed to analyze the immune infiltration levels in OA synovium and cartilage tissues, respectively. A total of 131 intersection genes were screened. These genes were mainly enriched in the osteoclast differentiation and PI3K-Akt signaling pathways. Then, eight OA-related hub genes were further identified, including JUN, MYC, VEGFA, ATF3, NR4A1, BTG2, DUSP1, and JUNB. ROC curve analysis showed the area under the curve of these eight genes was > 0.6 in another OA dataset, suggesting their feasible capacity for predicting OA. Finally, we found that NR4A1 and BTG2 might be involved in multiple inflammatory responses of OA tissues. Our study identified some OA-related hub genes and revealed novel insights into the biological mechanism of OA, which provided a theoretical foundation for further experimental study.

Does the hepatitis C virus affect the outcomes of total joint arthroplasty? A meta-analysis of ten studies.

BACKGROUND: It is estimated that 3%-8% of orthopedic patients, many of whom may undergo lower extremity total joint arthroplasty (TJA), are infected with hepatitis C virus. However, the impact of this virus on total joint arthroplasty is still undefined. METHODS: Eligible studies were searched from electronic databases including PubMed, Web of Science, CNKI and OVID. Two researchers performed data extraction from eligible independently. Quality parameters and risk of bias in the included studies were assessed according to Cochrane's guidelines. The pooled Standardized Mean Difference (SMD) with a 95%CI was used to assess the outcomes of total joint arthroplasty in patients with the hepatitis C virus. RESULTS: A total of 28 articles related to hepatitis C virus and total joint arthroplasty were reviewed. All clinical studies were eliminated and six articles containing ten studies eventually satisfied the eligibility criteria for this study. The pooled analysis showed hepatitis C had a higher complications rate than non-hepatitis C, with the pooled HR values of 1.55 (95%CI = 1.11-2.17, p = 0.01). As for THA, an overall pooled HR value (HR = 2.21, 95%CI = 1.19-4.10, p = 0.012) was obtained, indicating that patients with hepatitis C virus had a higher revision rate than non-hepatitis C. The infection rate was different between hepatitis C patients and non-hepatitis C controls (HR = 1.29, 95% = 1.17-1.44, P = 0.00). The combined analysis revealed a significantly longer length of hospital stay in patients with hepatitis C virus (HR = 0.88, 95%CI = 0.54-1.21, p = 0.000). CONCLUSIONS: This is the first systematic review and meta-analysis investigating the impact of hepatitis virus on total joint arthroplasty. Based on this meta-analysis, we can draw a conclusion that the patients with hepatitis C virus have higher rates of complication, infection, and revision compared to patients with non-hepatitis virus. Besides, hepatitis C infected patients require a significant longer hospital stay than patients without hepatitis.

Altered Coupling Between Resting-State Cerebral Blood Flow and Functional Connectivity Strength in Cervical Spondylotic Myelopathy Patients.

Background: Changes in regional neural activity and functional connectivity in cervical spondylotic myelopathy (CSM) patients have been reported. However, resting-state cerebral blood flow (CBF) changes and coupling between CBF and functional connectivity in CSM patients are largely unknown. Methods: Twenty-seven CSM patients and 24 sex/age-matched healthy participants underwent resting-state functional MRI and arterial spin labeling imaging to compare functional connectivity strength (FCS) and CBF between the two groups. The CBF-FCS coupling of the whole gray matter and specific regions of interest was also compared between the groups. Results: Compared with healthy individuals, CBF-FCS coupling was significantly lower in CSM patients. The decrease in CBF-FCS coupling in CSM patients was observed in the superior frontal gyrus, bilateral thalamus, and right calcarine cortex, whereas the increase in CBF-FCS coupling was observed in the middle frontal gyrus. Moreover, low CBF and high FCS were observed in sensorimotor cortices and visual cortices, respectively. Conclusion: In general, neurovascular decoupling at cortical level may be a potential neuropathological mechanism of CSM.

Cross-talk Between Histone and DNA Methylation Mediates Bone Loss in Hind Limb Unloading.

Bone loss induced by mechanical unloading is a common skeletal disease, but the precise mechanism remains unclear. The current study investigated the role of histone methylation, a key epigenetic marker, and its cross-talk with DNA methylation in bone loss induced by mechanical unloading. The expression of G9a, ubiquitin-like with PHD and ring finger domains 1 (UHRF1), and DNA methylation transferase 1 (DNMT1) were increased in hind limb unloading (HLU) rats. This was accompanied by an increased level of histone H3 lysine 9 (H3K9) di-/tri-methylation at lncH19 promoter. Then, alteration of G9a, DNMT1, or UHRF1 expression significantly affected lncH19 level and osteogenic activity in UMR106 cells. Osteogenic gene expression and matrix mineralization were robustly promoted after simultaneous knockdown of G9a, DNMT1, and UHRF1. Furthermore, physical interactions of lncH19 promoter with G9a and DNMT1, as well as direct interactions among DNMT1, G9a, and UHRF1 were detected. Importantly, overexpression of DNMT1, G9a, or UHRF1, respectively, resulted in enrichment of H3K9me2/me3 and 5-methylcytosine at lncH19 promoter. Finally, in vivo rescue experiments indicated that knockdown of DNMT1, G9a, or UHRF1 significantly relieved bone loss in HLU rats. In conclusion, our research demonstrated the critical role of H3K9 methylation and its cross-talk with DNA methylation in regulating lncH19 expression and bone loss in HLU rats. Combined targeting of DNMT1, G9a, and UHRF1 could be a promising strategy for the treatment of bone loss induced by mechanical unloading. © 2021 American Society for Bone and Mineral Research (ASBMR).