Understanding the role of Type 1 diabetes mellitus in osteoarthritis
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE198836 | GEO | 2022/03/17
REPOSITORIES: GEO
Similar Datasets
Project description:Type 1 diabetes mellitus (T1DM) affects 9.5% of the population. T1DM is characterized by severe insulin deficiency that causes hyperglycemia and leads to several systemic effects. T1DM has been suggested as a risk factor for articular cartilage damage and loss, which could expedite the development of osteoarthritis (OA). OA represents a major public health challenge by affecting 300 million people globally, yet very little is known about the correlation between T1DM and OA. In this study we aimed to understand the role of T1DM in OA by evaluating whether pre-existing T1DM exacerbates the development of knee post traumatic osteoarthritis (PTOA).
2022-03-17 | GSE198837 | GEO
Project description:Injuries to the anterior cruciate ligament (ACL) often result in post-traumatic osteoarthritis (PTOA). PTOA accounts for ~12% of all osteoarthritis (OA) cases, yet the mechanisms contributing to OA after joint injury are not well understood. To better understand the molecular mechanisms behind PTOA development following ACL injury, we profiled ACL injury-induced gene expression changes in knee joints of three mouse strains with varying susceptibility to PTOA: STR/ort (highly susceptible), C57BL/6 (moderately susceptible) and super-healer MRL/MpJ (not susceptible) and identified genes differentially expressed between these strains at 0-day [before injury], 1-day, 1-week, and 2-weeks post-injury. This study highlights many new potential therapeutic targets and OA biomarkers.
2018-11-28 | GSE112641 | GEO
Project description:Osteoarthritis (OA) of the hand is a common disease resulting in pain and impaired function. The pathogenesis of hand OA (HOA) is elusive and models to study it have not been described so far. Culture of chondrocytes is a model to study the development of cartilage degeneration, which is a hallmark of OA and well established in OA of the knee and hip. In the current study we investigated the feasibility human chondrocyte culture derived from proximal interphalangeal (PIP) finger joints of dissecting room cadavers. Index and middle fingers without signs of osteoarthritis were obtained from 30 cadavers using two different protocols. Hyaline cartilage from both articulating surfaces of the proximal interphalangeal (PIP) joint was harvested and digested in collagenase. Cultured chondrocytes were monitored for contamination, viability, and expression of chondrocyte specific genes. Chondrocytes derived from knee joints of the cadavers were cultured under identical conditions. Gene expression comparing chondrocytes from PIP and knee joints was carried out using Affymetrix GeneChip Human 2.0 ST arrays. The resulting differentially expressed genes were validated by real-time PCR and immunohistochemistry.Chondrocytes harvested up to 101 hours after death of the donors were viable. mRNA expression of collagen 2A1, aggrecan and Sox9 was significantly higher in chondrocytes as compared to cultured fibroblasts. Comparison of gene expression by chondrocytes from PIP and knee joints yielded 528 differentially expressed genes. Chondrocytes from the same joint region had a higher grade of similarity than chondrocytes of the same individual. These results were validated using real-time PCR and immunohistochemistry.We demonstrate for the first time a reliable method for culture of chondrocytes derived from PIP joints. PIP chondrocytes show a specific gene expression pattern and could be used as tool to study cartilage degeneration in HOA. Three samples of cultured chondrocytes from knee and proximal interphalangeal finger joints were compared. Gene expression of the four most differentially regulated genes was confirmed by real-time PCR in 10 independent samples.
2016-07-03 | E-GEOD-68038 | biostudies-arrayexpress
Project description:Osteoarthritis (OA) is the most common joint disease, affecting over 300 million people world-wide. Accumulating evidence attests to the important roles of immune system in OA pathogenesis. Understanding the role of various immune cells in joint degeneration or joint repair after injury is helpful for improving therapeutic strategies for treating OA. Post-traumatic osteoarthritis (PTOA) develops in ~50% of individuals who have experienced an articular trauma like an anterior cruciate ligament (ACL) rupture. Here, using highly sensitive single-cell RNA sequencing technology, we delineated the temporal dynamics of immune cell accumulation in the mouse knee joint after ACL rupture.
2022-07-18 | GSE200843 | GEO
Project description:Osteoarthritis (OA) of the hand is a common disease resulting in pain and impaired function. The pathogenesis of hand OA (HOA) is elusive and models to study it have not been described so far. Culture of chondrocytes is a model to study the development of cartilage degeneration, which is a hallmark of OA and well established in OA of the knee and hip. In the current study we investigated the feasibility human chondrocyte culture derived from proximal interphalangeal (PIP) finger joints of dissecting room cadavers. Index and middle fingers without signs of osteoarthritis were obtained from 30 cadavers using two different protocols. Hyaline cartilage from both articulating surfaces of the proximal interphalangeal (PIP) joint was harvested and digested in collagenase. Cultured chondrocytes were monitored for contamination, viability, and expression of chondrocyte specific genes. Chondrocytes derived from knee joints of the cadavers were cultured under identical conditions. Gene expression comparing chondrocytes from PIP and knee joints was carried out using Affymetrix GeneChip Human 2.0 ST arrays. The resulting differentially expressed genes were validated by real-time PCR and immunohistochemistry.Chondrocytes harvested up to 101 hours after death of the donors were viable. mRNA expression of collagen 2A1, aggrecan and Sox9 was significantly higher in chondrocytes as compared to cultured fibroblasts. Comparison of gene expression by chondrocytes from PIP and knee joints yielded 528 differentially expressed genes. Chondrocytes from the same joint region had a higher grade of similarity than chondrocytes of the same individual. These results were validated using real-time PCR and immunohistochemistry.We demonstrate for the first time a reliable method for culture of chondrocytes derived from PIP joints. PIP chondrocytes show a specific gene expression pattern and could be used as tool to study cartilage degeneration in HOA.
2016-01-01 | GSE68038 | GEO
Project description:Large scale RNA-Seq analysis was performed to investigate the transcriptomic response to osteoarthritis in cartilage and investigate potential subgroups of patients. Data were collected from intact knee cartilage (posterior lateral condyle) from at total of 60 patients with osteoarthritis (OA) following total knee replacement and 10 control non-OA patients following amputation.
2017-12-13 | E-MTAB-6266 | biostudies-arrayexpress
Project description:Osteoarthritis (OA) and rheumatoid arthritis (RA) are joint diseases that are associated with pain and lost quality of life. No disease modifying OA drugs are currently available. RA treatments are better established but are not always effective and can cause immune suppression. Here, an MMP13-selective siRNA conjugate (Albumin-binding siMMP13<(EG18L)2) was developed that, when delivered intravenously, docks onto endogenous albumin and promotes preferential accumulation in articular cartilage and synovia of post-traumatic OA (PTOA) and RA (K/BxN) joints. MMP13 expression was diminished upon intravenous delivery of MMP13 siRNA conjugates, consequently decreasing multiple histological and molecular markers of disease severity, while also reducing clinical manifestations such as swelling (RA) and joint pressure sensitivity (RA and OA). Importantly, MMP13 silencing provided more comprehensive OA treatment efficacy than standard of care (steroids) or experimental MMP inhibitors. These data demonstrate the utility of albumin ‘hitchhiking’ for drug delivery to arthritic joints, and establish the therapeutic utility of systemically delivered anti-MMP13 siRNA conjugates in OA and RA.
2023-05-30 | GSE233714 | GEO
Project description:Objectives : Joint pain causes a significant morbidity in osteoarthritis (OA). The synovium as an innervated joint structure might contribute to the peripheral pain in OA. Methods : We used a hypothesis-free next generation RNA sequencing to study protein coding and small non-coding transcriptomes in knee synovial tissues of OA patients (n=10) with high and low knee pain (evaluated by visual analogue scale) followed by Gene Ontology (GO) and pathway analyses and integration of mRNAs and small RNAs data sets. Results : We showed that 33 protein-coding genes and 35 small RNAs were differentially expressed in the knee synovium of patients with high compared to low intensity knee pain, with 30 mRNAs and 14 small RNAs being upregulated and 2 mRNAs and 21 small RNAs being downregulated. Top enriched genes, such as SDIM1 and CPE encode neuronal proteins that share molecular properties with neurotrophic factor BDNF and promote neuronal survival under cellular stress, and OTOF participates in calcium-dependent synaptic exocytosis and modulation of GABAergic activity. TrkB was enriched in several gene networks, suggesting its key role in pain-related transcriptional changes in OA joint. Downregulation of PTX3 in high pain group supports an argument that inflammation and pain are independent processes in symptomatic knee OA. MiR-146a-3p and miR150 appeared as the microRNA candidates in the pathogenesis of OA-related knee pain. Conclusions : Here we uncovered the molecular complexity of pain-related transcriptome changes in the synovium of knee joints in osteoarthritis. We identified new molecular candidates in OA pain setting a firm ground for future mechanistic studies and drug discovery in OA.
2018-11-05 | GSE99662 | GEO
Project description:Objective: To quantify gene expression changes in the synovium of osteoarthritis-affected joints in an equine metacarpophalangeal joint (MCPJ) chip model specifically designed to recapitulate early post-traumatic osteoarthritis (PTOA). Design: Synovial samples were collected arthroscopically from the MCPJ of 11 adult horses before (pre-OA) and after (OA) surgical induction of osteoarthritis and from sham-operated joints. Briefly, in this model, an osteochondral fragment is created in one randomly chosen MCPJ at the proximal dorsomedial aspect of the first phalanx. The fragment is replaced in the fragment bed after creation so that subchondral bone is not exposed to the opposing cartilage surface. The opposite MCPJ is sham-operated. After a two week recover period, the horses are treadmill-exercised for 14 weeks and then the osteochondral fragment is removed (16 weeks after creation). Synovial tissue samples were collected arthroscopically from the MCPJ of eleven adult horses before (pre-OA) and 16 weeks after (OA) experimental induction of OA as well as from the sham-operated joints (sham). After sequencing of synovial RNA, Salmon was used to quasi-map reads to the reference genome and quantify transcript abundances. Differential expression analysis was performed with the limma-treat method using a fold-change cutoff of 1.1. Functional annotation was performed with PANTHER and Reactome at FDR < 0.05. Results: RNA was successfully extracted from 28 samples (6 pre-OA, 11 OA, 11 sham). Sequencing yielded 15.7-29.4 million paired-end reads per sample. “Sham” and “pre-OA” were not different and were grouped. 321 genes were upregulated and 351 genes were downregulated in OA synovium compared to unaffected. Gene ontology (GO) terms related to extracellular matrix (ECM) organization and growth factor binding were overrepresented among differentially expressed genes. There were 20 significantly enriched pathways; these included pathways involved in ECM turnover, O-glycosylation of TSR domain-containing proteins, and growth factor signaling. Conclusions: Most enriched pathways and overrepresented GO terms reflect a state of high metabolic activity and tissue turnover in OA-affected tissue, suggesting efforts at healing and restoring homeostasis. Limitations of this study include a small sample size and capture of a single point post-injury. Differentially expressed genes falling within key pathways may represent potential diagnostic markers or therapeutic targets for PTOA.
2020-12-09 | GSE144031 | GEO
Project description:The main cause of morbidity and mortality in diabetes mellitus (DM) are cardiovascular complications. Diabetic cardiomyopathy (DCM) remains incompletely understood. Animal models have been crucial in exploring DCM pathophysiology while identifying potential therapeutic targets. Streptozotocin (STZ) has been widely used to produce experimental models of both type 1 and type 2 DM (T1DM and T2DM). Here we compared these two models for their effects on cardiac structure, function, and transcriptome. Different doses of STZ and different diet chows were used to generate T1DM and T2DM in C57BL/6J mice. Normal euglycemic and non-obese sex and age-matched mice served as controls (CTRL). Immunohistochemistry, RT-PCR, and RNA-Seq were employed to compare hearts from the three animal groups. STZ-induced T1DM and T2DM differently affect left ventricular function and myocardial performance. T1DM displays an exaggerated apoptotic cardiomyocyte (CM) death and reactive hypertrophy and fibrosis along with increased cardiac oxidative stress, CM DNA damage and senescence when compared to T2DM mice. T1DM and T2DM differently affect whole cardiac transcriptome. In conclusion, STZ-induced T1DM and T2DM mouse models show significant differences in cardiac remodeling, function and whole transcriptome. These differences could be of key relevance when choosing an animal model to study specific features of DCM.
2023-02-20 | E-MTAB-12558 | biostudies-arrayexpress