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: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:Age as the primary rise factor could be play an important role in incidence and development of osteoarthritis. A few studies have confirmed some tissue specific lncRNA were associated with development of osteoarthritis. But if age related lncRNA would be involved in pivotal post-transcriptional gene regulation in osteoarthritis is unclear. In view of this, we have an idea that several age-related lncRNA would be screened from the rat knee cartilage at different development ages by lncRNAs Microarray analysis. We used microarrays to detail the global programme of gene expression underlying the rat knee cartilage and identified distinct classes of age-related lncRNA during this process. The rat knee articular cartilage were selected at successive stages of the rat developmental for RNA extraction and hybridization on Affymetrix lncRNA arrays. We sought to obtain homogeneous populations of cartilage at each developmental stage in order to increase the temporal resolution of expression profiles. To that end, we hand-selected cartilage according to the rat developmental stages, i.e. seven time-points: newborn (T0), youth(T1), adult (T2), early-stage elderly(T3) and latter-stage elderly(T4).
Project description:Patients with anterior cruciate ligament (ACL) tears have a significantly increased risk for developing knee osteoarthritis. These injuries often result in a knee effusion in response to the injury. Early changes in these effusions could be informative regarding initial steps in the development of post traumatic osteoarthritis. The purpose of this study was to test the hypothesis that the proteomics of knee synovial fluid changes over time following ACL injury.