Identification and Validation of Potential Ferroptosis-Related Genes in Glucocorticoid-Induced Osteonecrosis of the Femoral Head.

Background and Objectives. Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a serve complication of long-term administration of glucocorticoids. Previous experimental studies have shown that ferroptosis might be involved in the pathological process of GIONFH. The purpose of this study is to identify the ferroptosis-related genes and pathways of GIONFH by bioinformatics to further illustrate the mechanism of ferroptosis in SONFH through bioinformatics analysis. Materials and Methods. The GSE123568 mRNA expression profile dataset, including 30 GIONFH samples and 10 non-GIONFH samples, was downloaded from the Gene Expression Omnibus (GEO) database. Ferroptosis-related genes were obtained from the FerrDb database. First, differentially expressed genes (DEGs) were identified between the serum samples from GIONFH cases and those from controls. Ferroptosis-related DEGs were obtained from the intersection of ferroptosis-related genes and DEGs. Only ferroptosis DEGs were used for all analyses. Then, we conducted a Kyoto encyclopedia of genome (KEGG) and gene ontology (GO) pathway enrichment analysis. We constructed a protein-protein interaction (PPI) network to screen out hub genes. Additionally, the expression levels of the hub genes were validated in an independent dataset GSE10311. Results. A total of 27 ferroptosis-related DEGs were obtained between the peripheral blood samples of GIONFH cases and non-GIONFH controls. Then, GO, and KEGG pathway enrichment analysis revealed that ferroptosis-related DEGs were mainly enriched in the regulation of the apoptotic process, oxidation-reduction process, and cell redox homeostasis, as well as HIF-1, TNF, FoxO signaling pathways, and osteoclast differentiation. Eight hub genes, including TLR4, PTGS2, SNCA, MAPK1, CYBB, SLC2A1, TXNIP, and MAP3K5, were identified by PPI network analysis. The expression levels of TLR4, TXNIP and MAP3K5 were further validated in the dataset GSE10311. Conclusion. A total of 27 ferroptosis-related DEGs involved in GIONFH were identified via bioinformatics analysis. TLR4, TXNIP, and MAP3K5 might serve as potential biomarkers and drug targets for GIONFH.

Serum nicotinamide phosphoribosyltransferase as a novel biomarker for non-traumatic osteonecrosis of the femoral head.

OBJECTIVE: The aim of this study was to investigate the potential role of serum nicotinamide phosphoribosyltransferase (NAMPT) in non-traumatic osteonecrosis of femoral head (NONFH). METHODS: A total of 113 NONFH patients and 81 healthy individuals were included in this study. The NAMPT levels in serum were measured by a commercial enzyme-linked immunosorbent assay kit. Radiographic progression was determined using Association Research Circulation Osseous (ARCO) classification system. Clinical severity was assessed by Harris hip score (HHS) and visual analogue scale (VAS). Correlations between serum NAMPT and radiographic progression as well as clinical severity were evaluated statistically. Receiver operating characteristic (ROC) curves were performed to evaluate the diagnostic values of NAMPT in NONFH potential and disease severity. RESULTS: The serum NAMPT levels in NONFH patients were significantly lower than that in healthy controls. There were no significant differences among alcohol-induced group, steroids-induced group, and idiopathic group. NONFH patients with ARCO stage 4 had significant lower serum NAMPT levels in comparisons with ARCO stage 3 and 2, respectively. Lower serum NAMPT levels were also observed in bilateral NONFH cases compared with cases with unilateral NONFH. In addition, serum NAMPT was negatively correlated with ARCO stages and VAS scores, and positively correlated with HHS. ROC curve analysis indicated that serum NAMPT may serve as a novel biomarker for diagnosing early NONFH and for monitoring disease severity. CONCLUSIONS: Our results suggest that serum NAMPT may serve as a novel biomarker for NONFH potential and disease severity.

A novel serological biomarker are associated with disease severity in patients with osteoarthritis.

BACKGROUND AND AIM: Apolipoprotein D (ApoD) is a 25-30 kDa glycoprotein, as a distinct component of the human plasma lipoprotein system. Its known biological functions are mainly related to lipid metabolism. The purpose of this study was to explore the potential role of ApoD concentration in knee osteoarthritis (KOA). METHODS: This study was performed in a population of 113 KOA subjects and 97 healthy controls. Serum ApoD was detected using the commercial ELISA kit (Cusabio, Wu Han, China, Cat No. CSB-EL001935HU). Radiographic progression was evaluated using Kellgren-Lawrence (KL) classification. The clinical severity of KOA was assessed by visual analog score (VAS), Hospital for special surgery (HSS) knee score disease duration and TNF-α. Receiver-operating characteristic (ROC) curve was performed to test the potential diagnostic value of ApoD in radiographic progression. RESULTS: The serum ApoD level of patients with KOA was significantly lower than that of healthy controls. The serum ApoD level was negatively correlated with KL grades, VAS score, disease duration, TNF-α concentrations. On the contrary, it was positively correlated with HSS score. However, there was no correlation between this serological indicator and which side was affected. ROC curve analysis indicated that attenuated serum ApoD could serve as an appropriate biomarker concerning the diagnosis of KOA. CONCLUSIONS: Serum ApoD concentration was correlated with the presence and severity of KOA.