Expression data from the rat knee articular cartilage at different developmental stages
Ontology highlight
ABSTRACT: Age as the primary rise factor could be play an important role in incidence and development of osteoarthritis. Several studies have confirmed some tissue specific microRNA were associated with development of osteoarthritis. But if age related microRNA or miRNA cluster 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 miRNAs would be screened from the rat knee cartilage at different development ages by miRNAs 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 miRNAs during this process. The rat knee articular cartilage were selected at successive stages of the rat developmental for RNA extraction and hybridization on Affymetrix microarrays. 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), childhood (T1), youth(T2), adult (T3), middle-aged (T4) early-stage elderly(T5) and latter-stage elderly(T6). The objective of the study is to identify miRNA profile of knee articular cartilage at different developmental ages in rats. Total RNA were extracted from the knee articular cartilage of Sprague-Dawley rats at postnatal day 0(T0), week1(T1), week 4(T2), mon3(T3), mon 6(T4), mon 12(T5), and mon 18(T6). The microRNA profile in the specimens was detected with the Affymetrix GeneChip® miRNA 3.0 Array.
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:Age as the primary rise factor could be play an important role in incidence and development of osteoarthritis. Several studies have confirmed some tissue specific microRNA were associated with development of osteoarthritis. But if age related microRNA or miRNA cluster 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 miRNAs would be screened from the rat knee cartilage at different development ages by miRNAs 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 miRNAs during this process.
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.
Project description:Proteolytic destruction of articular cartilage is a major pathogenic mechanism in osteoarthritis (OA), but was not previously investigated on a proteome-wide scale. We sought to define the human knee OA cartilage degradome.
Project description:Single-cell transcriptomics analysis of human knee articular cartilage tissue to present a comprehensive transcriptome atlas and osteoarthritis-critical cell populations.
Project description:Osteoarthritis is a common joint disorder that causes debilitating conditions among the elderly. Risk factors of osteoarthritis include age, which is often associated with the thinning of articular cartilage. We generated conditional knockout mice that lack salt-inducible kinase 3 (Sik3) specifically in chondrocytes after birth by tamoxifen administration. Deletion of Sik3 at 2 or 8 weeks after birth increased the thickness of articular cartilage by increasing the chondrocyte population. Additionally, Sik3 deletion protected cartilage against osteoarthritis development. We identified the edible Pteridium aquilinum ingredient, pterosin B, as a compound that inhibits the Sik3 pathway. Intraarticular injection of pterosin B protected cartilage against osteoarthritis development. Sik3 deletion or pterosin B treatment inhibited activation of the hypertrophic program through the histone deacetylase 4 (Hdac4) pathway, increased Prg4 expression in chondrocytes, and protected cartilage against osteoarthritic attack. Collectively, our results suggest Sik3 is a regulator that regulates homeostasis of articular cartilage thickness and a target for treatment of osteoarthritis, and that pterosin B can be the lead compound for relevant drugs.
Project description:Hui2014 - Age-related changes in articular
cartilage
This model is described in the article:
Oxidative changes and
signalling pathways are pivotal in initiating age-related
changes in articular cartilage
Wang Hui1, David A Young1, Andrew D
Rowan1, Xin Xu2, Tim E Cawston1, Carole J Proctor1,3
Annals of the Rheumatic Diseases
Abstract:
Objective: To use a computational approach to investigate
the cellular and extracellular matrix changes that occur with
age in the knee joints of mice. Methods: Knee joints from an
inbred C57/BL1/6 (ICRFa) mouse colony were harvested at
3–30?months of age. Sections were stained with H&E,
Safranin-O, Picro-sirius red and antibodies to matrix
metalloproteinase-13 (MMP-13), nitrotyrosine, LC-3B, Bcl-2, and
cleaved type II collagen used for immunohistochemistry. Based
on this and other data from the literature, a computer
simulation model was built using the Systems Biology Markup
Language using an iterative approach of data analysis and
modelling. Individual parameters were subsequently altered to
assess their effect on the model. Results: A progressive loss
of cartilage matrix occurred with age. Nitrotyrosine, MMP-13
and anaplastic lymphoma kinase (ALK1) staining in cartilage
increased with age with a concomitant decrease in LC-3B and
Bcl-2. Stochastic simulations from the computational model
showed a good agreement with these data, once transforming
growth factor-? signalling via ALK1/ALK5 receptors was
included. Oxidative stress and the interleukin 1 pathway were
identified as key factors in driving the cartilage breakdown
associated with ageing. Conclusions: A progressive loss of
cartilage matrix and cellularity occurs with age. This is
accompanied with increased levels of oxidative stress,
apoptosis and MMP-13 and a decrease in chondrocyte autophagy.
These changes explain the marked predisposition of joints to
develop osteoarthritis with age. Computational modelling
provides useful insights into the underlying mechanisms
involved in age-related changes in musculoskeletal tissues.
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Project description:Background: Meniscus tears are the most common injury in the knee and are associated with an increased risk of osteoarthritis (OA). The molecular profile of knees with meniscus tears is not well-studied. Therefore, to advance our understanding of the early response of the knee to injury, we compared the gene expression profile of meniscus and articular cartilage within the same knees following meniscus injury. Hypothesis/Purpose: To identify differences between the molecular signatures of meniscus and articular cartilage from knees with intact articular cartilage undergoing arthroscopic partial meniscectomy. Study Design: Descriptive laboratory study Methods: Patients (n=12) with a known isolated medial meniscus tear without any knee chondrosis or radiographic OA were consented prior to surgery. During arthroscopic partial meniscectomy, a sample of their injured meniscus and a sample of their articular cartilage off the medial femoral condyle were procured. The transcriptome signatures, as measured through Affymetrix microarray, were compared between the two tissues and underlying biological processes were explored computationally. Results: 3566 gene transcripts were differentially expressed between meniscus and articular cartilage. Gene transcripts down-regulated in articular cartilage were associated with extracellular matrix organization, wound healing, cell adhesion, and chemotaxis. Gene transcripts up-regulated in articular cartilage were associated with blood vessels morphogenesis and angiogenesis. Examples of individual genes with significant differences in expression between the two tissues include IBSP (23.76 fold; P < 0.001), upregulated in meniscus, and TREM1 (3.23 fold; P = 0.006), upregulated in meniscus. Conclusion: The meniscus and articular cartilage have distinct gene expression profiles in knees with meniscus tears and intact articular cartilage. Total RNA obtained from injured meniscus and normal articular cartilage from patients undergoing partial meniscectomy.
Project description:The current study compared the transcriptomes of knee joint articular cartilage and synovium in a large animal model one year following posttraumatic osteoarthritis induction and multiple surgical treatment modalities.