Dataset Information

Collagen type V a2 (COL5A2) is decreased in steroid-induced necrosis of the femoral head.

ABSTRACT: Collagen is essential for bone adhesion and formation. In the present study, proteomic analysis suggested that collagen type V a2 (COL5A2) was significantly decreased in the necrotic area of patients with steroid-induced necrosis of the femoral head (ONFH). In vitro, the effects of methylprednisolone (MP) on the proliferation and differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) were investigated. The expression of the osteogenic-related proteins, Runx2, alkaline phosphatase (ALP), osteocalcin (OC) and COL5A2 was significantly downregulated post-MP treatment. In vivo analyses revealed that post-MP treatment, rats showed typical signs of ONFH by micro-CT scanning and hematoxylin and eosin (H&E) staining. Immunohistochemical staining demonstrated that the expression of COL5A2 and vascular endothelial growth factor (VEGF) was significantly decreased post-MP treatment. In conclusion, the expression COL5A2 was lower in patients with steroid-induced ONFH, hence COL5A2 may be a promising therapeutic target for steroid induced ONFH treatment.

SUBMITTER: Yang F

PROVIDER: S-EPMC6129523 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Collagen type V a2 (COL5A2) is decreased in steroid-induced necrosis of the femoral head.

Yang Fan F Luo Pengbo P Ding Hao H Zhang Changqing C Zhu Zhenhong Z

American journal of translational research 20180815 8

Collagen is essential for bone adhesion and formation. In the present study, proteomic analysis suggested that collagen type V a2 (COL5A2) was significantly decreased in the necrotic area of patients with steroid-induced necrosis of the femoral head (ONFH). <i>In vitro</i>, the effects of methylprednisolone (MP) on the proliferation and differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) were investigated. The expression of the osteogenic-related proteins, Runx2, alkalin ...[more]

PMID: 30210685

Similar Datasets

Project description:The steriod-induced necrosis of femoral head(SINFH) is a serious clinical problem and the underlying mechanism of this disease remains unknown. As its etiology and pathogenesis are not clear, there hasn’t been an effective treatment yet. In-depth studies on its pathogenesis will provide important information for the prevention and treatment of this devastated disease. Animal model researches are helpful to a better understanding of its etiology and pathogenesis, to early diagnosis and treatments and provide the basis for clinical treatment It has been proved that the occurrence of SINFH is related to gene itself and its polymorphism. These studies, in which only one or a few genes were investigated, could not provide a comprehensive understanding to the pathogenesis of SINFH. We used microarrays to compare the gene expression profile of SINFH rats with that of normal rats and identified gene expression changes between SINFH rats and normal rats. Adult healthy male Wistar rats(body weight 200±10g) were randomly divided into control and experimental groups. All the rats were given injection of E. coli endotoxin at a dose of 20μg/kg body weight into abdominal cavity for two times with a 24 hour interval. 24 hours after the second administration of E. coli endotoxin, methylprednisolone 40mg/kg was administered into the left gluteus muscle of experimental group rats for three times with a 24 hour interval. Rats were then killed 6 weeks after steroid administration. In experiment, immediately after death the left femoral heads were isolated. Femoral heads were used for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain the gene expression profile of SINFH rats and that of normal rats in order to identified gene expression changes between SINFH rats and normal rats by comparing the gene expression profile of SINFH rats with that of normal rats. To that end, we have established the gene expression profiles of normal and SINFH disease of rat femoral head and found out differentially expressed genes.

Project description:Objective To investigate the differential expression of exosomal miRNAs in the bone marrow tissue of Modified Qing’ E Formula (MQEF) on steroid-induced ischemic necrosis of the femoral head (INFH) model. Methods Steroid hormones were used to establish the INFH model and treated with MQEF. After successful modeling, femoral tissue exosomes were isolated for miRNA sequencing to obtain femoral tissue exosomal differential miRNAs. By GO analysis and KEGG analysis of the differential genes in both groups, the major exosomal miRNAs of MQEF exerting anti-INFH as well as the major signaling pathways were identified. Next, a quantitative metabolomic validation of MQEF with broad targeting was performed to obtain the main active components of MQEF and to perform biological analysis and signaling pathway prediction of the active components by network pharmacology. Finally, the sequencing results were validated by using RT-qPCR. The results of miRNA sequencing were verified by double examination of network pharmacology and RT-qPCR, and the exosomal miRNAs regulated by the anti-INFH effect of MQEF and the specific signaling pathway of the effect were clarified. Results A total of 65,389 target genes were predicted in the exosomes of two groups of mice, and 18 significant differentially expressed miRNAs were obtained, of which 14 were up-regulated and 4 down-regulated. GO enrichment analysis showed that these predicted target genes were enriched in 12371 biological processes, 1727 cell components, and 4112 molecular functions. KEGG analysis showed that the predicted miRNA target genes were annotated to 342 signal pathways, in which the highly enriched pathways closely related to bone metabolism were PI3K-Akt signal pathway, MAPK signal pathway, and Wnt signal pathway. The most significantly up-regulated miRNAs were miR-185-3p and miR-1b-5p and the most significantly down-regulated miRNAs were miR-129b-5p and miR-223-5p, of which the targeted genes were closely related to the PI3K-Akt signal pathway. MQEF aqueous decoction extract targeted metabolomics quantitatively combined with network pharmacology predicted targets also closely related to PI3K-Akt signaling pathway. Real-time quantitative PCR validation showed that miR-185-3p was up-regulated 7.2-fold and miR-129b-5p was down-regulated 2.2-fold in the treatment group, and the difference was significant (P < 0.05). Conclusions MQEF can regulate exosomal miRNA expression in steroid-induced INFH models, miR-185-3p or miR-129b-5p/PI3K-Akt signal axis may be part of the mechanism of MQEF against steroid-induced INFH.

Project description:(1) Background: Since the large-scale poultry industry has been established, femoral head necrosis (FHN) has always been a major leg disease in fast-growing broilers worldwide. Previous research suggested that cartilage homeostasis could be taken into consideration in the cause of FHN, but the evidence is insufficient. (2) Methods: One-day-old broiler chickens were randomly divided into three groups, 16 broilers per group. The birds in group L were injected intramuscularly with methylprednisolone (MP) twice a week for four weeks (12.5 mg·kg-1). The birds in group H were injected intramuscularly with MP (20 mg·kg-1·d-1) for 7 d (impulse treatment). The birds in group C were treated with sterile saline as a control group. Broilers were sacrificed at 42 and 56 d. Blood samples were collected from the jugular vein for ELISA and biochemical analysis. Bone samples, including femur, tibia, and humerus, were collected for histopathological analysis, bone parameters detection, and real-time quantitative PCR detection. (3) Results: The FHN broilers in group L and H both showed lower body weight (BW) and reduced bone parameters. In addition, the MP treatment resulted in reduced extracellular matrix (ECM) anabolism and enhanced ECM catabolism. Meanwhile, the autophagy and apoptosis of chondrocytes were enhanced, which led to the destruction of cartilage homeostasis. Moreover, the impulse MP injection increased the portion of birds with severer FHN, whereas the MP injection over a long period caused a more evident change in serum cytokine concentrations and bone metabolism indicators. (4) Conclusions: The imbalance of cartilage homeostasis may play a critical role in the development of FHN in broilers. FHN broilers induced by MP showed a more pronounced production of catabolic factors and suppressed the anabolic factors, which might activate the genes of the WNT signal pathway and hypoxia-inducible factors (HIFs), and then upregulate the transcription expression of ECM to restore homeostasis.

Dataset Information

Collagen type V a2 (COL5A2) is decreased in steroid-induced necrosis of the femoral head.

Publications

Collagen type V a2 (COL5A2) is decreased in steroid-induced necrosis of the femoral head.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets