Project description:Steroid-induced avascular necrosis of the femoral head (SANFH) is closely associated with the imbalance between adipogenic and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Additionally, epigenetic regulation plays a critical role in this process. Our previous research found that during BMSC adipogenic differentiation, C/EBPα enhances the histone H3K27 acetylation modification at the PPARγ promoter, promoting sustained adipogenic differentiation of BMSCs, suggesting that Histone deacetylases (HDACs) may play an important role in BMSC adipogenic differentiation. However, identifying specific HDAC target genes requires further investigation. This study combines cell experiments with clinical specimen experiments to screen specific HDAC genes involved in BMSC adipogenic differentiation and explore their preliminary functions. Our findings indicate that HDAC10 influences the progression of steroid-induced avascular necrosis of the femoral head by regulating BMSC adipogenic differentiation, possibly through its association with PPARγ histone acetylation. These discoveries provide promising directions for the treatment of steroid-induced avascular necrosis of the femoral head.
Project description:These libraries represent instances of Swarm rat chondrosarcoma tumors taken from different transplantation experiments. This series also contains one non-cancerous cartilage library made from rat normal growing femoral head cartilage as a comparative data point. Keywords: other
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:Knee osteoarthritis (KOA), as a degenerative multifactorial disease, affects the quality of life and mental health of patients, and also brings a huge socioeconomic burden. Treating synovitis have shown promise as anti-inflammatory therapeutics in mitigating OA symptoms and disease progression. Here, by analysing synovial single-cell sequencing (scRNA-seq) data from KOA, we found that synovial fibroblasts (FLS) in OA synovium showed a distinct pro-inflammatory phenotype. We collected synovial tissue from patients with clinical OA as well as from healthy donors, and histological examination was consistent with findings in scRNA-seq. Inspired by recent cross-tissue fibroblast lineage studies, we identified by sequencing that healthy FLS in synovial tissues share transcriptome-level similarities with dermal fibroblasts (DFb). Subsequently, we revealed the local as well as systemic distribution of intra-articular injected DFbs by constructing/extracting two types of rat fibroblasts (luciferase DFbs as well as GFP DFbs). The results demonstrate that DFbs can be locally retained in the synovium for up to three weeks following targeted engrafting on it. And intra-articular injection does not result in DFbs migration to vital organs or the occurrence of histological changes in these organs. A rat model of KOA was constructed by anterior cruciate ligament transection (ACLT) in order to study the therapeutic effect of DFbs on KOA. After injection, the rats showed improvement in painful gait. In addition, histological as well as imaging results showed reduced synovitis and improvement in articular cartilage. Finally we verified the protective effect of DFbs on cytokine-stimulated chondrocytes in a co-culture system.
Project description:These libraries represent instances of Swarm rat chondrosarcoma tumors taken from different transplantation experiments. This series also contains one non-cancerous cartilage library made from rat normal growing femoral head cartilage as a comparative data point. Keywords: other