Project description:Bone mineral density and structure candidate gene analysis in alcohol-non-preferring (NP), alcohol-preferring (P), congenic NP (NP.P) and congenic P (P.NP) rats Genetic mapping in alcohol-preferring (P) and alcohol-non-preferring (NP) rats has identified a major quantitative trait locus (QTL) in the region between q22 – q34 on chromosome (Chr) 4 for alcohol preference. In a separate genome-wide linkage study, using inbred Fischer 344 (F344) and Lewis (LEW) rats, several QTL linked to bone density and structure were identified at the same location suggesting that bone mass and strength genes might co-segregate with genes that regulate the alcohol preference trait. The aim of this study is to identify the genes segregating for skeletal phenotypes and alcohol trait in congenic P/NP rats. We compared bone mineral content (BMC), areal/volumetric bone mineral density (aBMD/vBMD) and biomechanical strength at different skeletal sites from 6-month-old inbred and congenic P/NP rats. Transfer of the NP Chr 4 QTL into P background significantly increased body weight but decreased BMC, aBMD/vBMD in whole body, cranium, femur, and lumbar vertebrae. On the other hand, transfer of P Chr 4 QTL into NP background significantly decreased body weight but increased BMC and aBMD in the same skeletal sites. Microarray analysis was performed from the femurs of 4-week-old rats (n = 5 per strain) using Affymetrix Rat Genome 230 2.0 arrays. A total of 53 genes, including 41 candidate genes and 12 predicted genes, were differentially expressed among all strains of rats with a false discovery rate (FDR) less than 10%. Several candidate genes from microarray analysis were found to be were strongly correlated (r2>0.50) with different skeletal phenotypes. Gene expression of top 3 candidate genes from microarray profiling was validated by quantitative real-time PCR (qRT-PCR). Ingenuity pathway analysis revealed relationships among the candidate genes related to bone metabolism including pathways related to beta-estradiol, tumor necrosis factor and androgen receptor. Keywords: Comparison of gene expression profiles between NP, P, NP.P and P.NP rats
Project description:Bone mineral density and structure candidate gene analysis in alcohol-non-preferring (NP), alcohol-preferring (P), congenic NP (NP.P) and congenic P (P.NP) rats; Genetic mapping in alcohol-preferring (P) and alcohol-non-preferring (NP) rats has identified a major quantitative trait locus (QTL) in the region between q22 â?? q34 on chromosome (Chr) 4 for alcohol preference. In a separate genome-wide linkage study, using inbred Fischer 344 (F344) and Lewis (LEW) rats, several QTL linked to bone density and structure were identified at the same location suggesting that bone mass and strength genes might co-segregate with genes that regulate the alcohol preference trait. The aim of this study is to identify the genes segregating for skeletal phenotypes and alcohol trait in congenic P/NP rats. We compared bone mineral content (BMC), areal/volumetric bone mineral density (aBMD/vBMD) and biomechanical strength at different skeletal sites from 6-month-old inbred and congenic P/NP rats. Transfer of the NP Chr 4 QTL into P background significantly increased body weight but decreased BMC, aBMD/vBMD in whole body, cranium, femur, and lumbar vertebrae. On the other hand, transfer of P Chr 4 QTL into NP background significantly decreased body weight but increased BMC and aBMD in the same skeletal sites. Microarray analysis was performed from the femurs of 4-week-old rats (n = 5 per strain) using Affymetrix Rat Genome 230 2.0 arrays. A total of 53 genes, including 41 candidate genes and 12 predicted genes, were differentially expressed among all strains of rats with a false discovery rate (FDR) less than 10%. Several candidate genes from microarray analysis were found to be were strongly correlated (r2>0.50) with different skeletal phenotypes. Gene expression of top 3 candidate genes from microarray profiling was validated by quantitative real-time PCR (qRT-PCR). Ingenuity pathway analysis revealed relationships among the candidate genes related to bone metabolism including pathways related to beta-estradiol, tumor necrosis factor and androgen receptor. Experiment Overall Design: Comparison of differentially expressed genes between 4q22-4q34 on chromosome 4 in NP, P, NP.P and P.NP rats.
Project description:Analysis of LBNF1 rat testes from controls, containing both somatic and all germ cell types and from irradiated rats in which all cells germ cells except type A spermatgogonia are eliminated. Results provide insight into distinguishing germ and somatic cell genes and identification of somatic cell genes that are upregulated after irradiation.
Project description:Male Sprague-Dawley rats were used to establish exhausted-exercise model by motorized rodent treadmill. Yu-Ping-Feng-San at doses of 2.18 g/kg was administrated by gavage before exercise training for 10 consecutive days. Quantitative proteomics was performed for assessing the related mechanism of Yu-Ping-Feng-San.
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.