Project description:The objective of this study was to determine which pathways are significantly regulated with age in sciatic and radial nerves, individually or considering the interaction term. We find a strong signature of the cholesterol biosynthesis pathway being downregulated with age in both nerves, however, this effect is significantly milder in the radial nerve. We collected both radial and sciatic nerves from 8 adult (8 months old) and 8 old (24 months old) rats.
Project description:Changes in gene expression during peripheral nerves aging, to the single cell level, are unkown. To explore possible age-related changes during healthy aging of peripheral nerves we compared snRNAseq of sciatic nerves from young adult (2-3 months old), senior adult (15-16 months old), and aged (20-30 month old mice.
Project description:Sciatic nerve ligation was performed on cohorts of 2-month and 24-month old animals. Resulting gene-expression data were generated from sciatic nerve 1 and 4 days after injury compared to naïve animals. Results show differences in sciatic nerve responses with normal aging. Total RNA taken from sciatic nerves from 2-month and 24-month old animals at either day 0, 1 and 4 after sciatic nerve crush injury.
Project description:The objective of this study was to determine which pathways are significantly regulated with age in sciatic and radial nerves, individually or considering the interaction term. We find a strong signature of the cholesterol biosynthesis pathway being downregulated with age in both nerves, however, this effect is significantly milder in the radial nerve.
Project description:Our objective was to identify early changes in gene expression related to the development of sarcopenia via transcriptomic profiling of aging sciatic nerves in vivo. Sciatic nerve mRNA profiles of C57BL/6JN mice aged 5 (n = 6), 18 (n = 5), 21 (n = 6), and 24 months (n = 5) old were generated by RNA sequencing using an Illumina HiSeq4000. The sequence reads that passed quality filters were mapped to the mouse reference genome using STAR and featureCounts. Differential expression analysis was performed using DESeq2. Differentially expressed genes were validated using quantitative reverse transcription PCR (qRT-PCR) using SYBR Green assays. We detected 51 significant differentially expressed genes in sciatic nerve of 18-month-old mice compared to 5-month-old mice. These genes were associated with the AMPK signaling pathway, biosynthesis and metabolic pathways, and circadian rhythm. These early molecular changes shed a new light on biological processes in peripheral nerve that may be implicated in sarcopenia initiation and pathogenesis. Future studies are warranted to confirm the disease modifying and/or biomarker potential of the key changes we report here.
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.