Sexual dimorphism of the synovial transcriptome underpins greater PTOA disease severity in male mice following joint injury
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE271903 | GEO | 2024/07/17
REPOSITORIES: GEO
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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:Despite ample evidence demonstrating that anterior cruciate ligament (ACL) and meniscus tears are associated with the development of knee osteoarthritis (OA), the contributing factors remain unknown. Synovial inflammation has recently been recognized as a pivotal factor in the pathogenesis of OA. However, there is a lack of data on synovial profiles after ACL or meniscus injuries, which may contribute to posttraumatic OA (PTOA). We performed RNA-seq of 3 inflamed synovial biopsy samples vs 3 normal synovial biopsy samples following ACL and/or meniscus injuries. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein–protein interaction (PPI) analyses were performed to investigate mRNAs with significant differences between the inflamed and normal groups.Next, competing endogenous RNA (ceRNA) networks were constructed based on bioinformatics analyses and quantitative real-time polymerase chain reaction (RT–PCR) results. The association of the identified DEGs with the levels of infiltrating immune cells was explored using Pearson correlation analysis in R software. We aimed to provide greater insights into molecular mechanisms and biologic pathways in synovitis that could regulate post-trauma osteoarthritis progression.
2022-11-18 | GSE213070 | GEO
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:36 Yucatan minipigs underwent anterior cruciate ligament (ACL) transection and were randomly assigned in equal numbers to no further treatment, reconstruction or ligament repair. Cartilage was harvested at 1 and 4 weeks post-operatively and histology and RNA-sequencing performed. The generated data served to identify the molecular pathophysiology present in early post-traumatic osteoarthritis (PTOA), as well as differences between surgical treatments.
2017-10-22 | E-MTAB-5879 | biostudies-arrayexpress
Project description:36 Yucatan minipigs underwent anterior cruciate ligament (ACL) transection and were randomly assigned in equal numbers to no further treatment, reconstruction or ligament repair. Peri-meniscal synovium was harvested at 1 and 4 weeks post-operatively and histology and RNA-sequencing performed. The generated data served to identify the molecular pathophysiology present in inflamed synovium during the early development of post-traumatic osteoarthritis (PTOA), as well as differences between surgical treatments.
2018-04-21 | E-MTAB-6664 | biostudies-arrayexpress
Project description:Yorkshire pigs received untreated unilateral ACL transection through a medial arthrotomy (INJ, n=6), transection with immediate injection of 20mg triamcinolone acetonide (TRI, n=6) or no surgery (CON, n=6). Synovial membranes were harvested two weeks after the injury in the lateral knee joint compartment. The whole biopsy was homogenised for RNA extraction. The objective of the experiment was to test if intraarticular corticosteroid injection mitigates injury-induced synovitis and collagen degradation after anterior cruciate ligament transection and to characterize the synovial response using the described perturbations in combination with a functional genomics approach.
2016-01-29 | E-MTAB-4294 | biostudies-arrayexpress
Project description:BACKGROUND. Although 25-hydroxyvitamin D (25(OH)D) concentrations ≥30ng/mL are known to reduce injury risk and boost strength, the influence on anterior cruciate ligament reconstruction (ACLR) outcomes remains unexamined. This study aimed to define the vitamin D signaling response to ACLR, assess the relationship between vitamin D status and muscle fiber cross-sectional area (CSA) and bone density outcomes, and discover vitamin D receptor (VDR) targets post-ACLR. METHODS. 21 young, healthy, physically active participants with recent ACL tears were enrolled (62% female; 17.8 ± 3.2 yr, BMI: 26.0 ± 3.5 kg/m2). Data were collected through blood samples, vastus lateralis biopsies, DXA bone density measurements, and isokinetic dynamometer measures at baseline, 1 week, 4 months, and 6 months post-ACLR. The biopsies facilitated CSA, western blot, RNA-seq, and VDR ChIP-seq analyses. RESULTS. ACLR surgery led to decreased circulating bioactive vitamin D and increased VDR and activating enzyme expression in skeletal muscle one week post-operation. Participants with <30 ng/mL 25(OH)D levels (n=13) displayed more significant quadriceps fiber CSA loss one week and 4 months post-ACLR than those with ≥30 ng/mL (n=8; p<0.01 for post-hoc comparisons; p=0.041 for time x vitamin D status interaction). RNA-seq and ChIP-seq data integration revealed genes associated with energy metabolism and skeletal muscle recovery, potentially mediating the impact of vitamin D status on ACLR recovery. No difference in bone mineral density (BMD) losses between groups was observed.
2023-12-31 | GSE243777 | GEO
Project description:RNA sequencing of the interface tissue after mouse anterior-cruciate ligament reconstruction (ACLR)
| PRJNA719787 | ENA
Project description:OBJECTIVE: To analyze genome-wide changes in chondrocyte gene expression in a surgically induced model of early osteoarthritis (OA) in rats, to assess the similarity of this model to human OA, and to identify genes and mechanisms leading to OA pathogenesis. METHODS: OA was surgically induced in 5 rats by anterior cruciate ligament transection and partial medial meniscectomy. Sham surgery was performed in 5 additional animals, which were used as controls. Both groups underwent 4 weeks of forced mobilization, 3 times per week. RNA was extracted directly from articular chondrocytes in the OA (operated), contralateral, and sham-operated knees. Affymetrix GeneChip expression arrays were used to assess genome-wide changes in gene expression. Expression patterns of selected dysregulated genes, including Col2a1, Mmp13, Adamts5, Ctsc, Ptges, and Cxcr4, were validated by real-time polymerase chain reaction, immunofluorescence, or immunohistochemistry 2, 4, and 8 weeks after surgery. RESULTS: After normalization, comparison of OA and sham-operated samples showed 1,619 differentially expressed probe sets with changes in their levels of expression >/=1.5-fold, 722 with changes >/=2-fold, 135 with changes >/=4-fold, and 20 with changes of 8-fold. Dysregulated genes known to be involved in human OA included Mmp13, Adamts5, and Ptgs2, among others. Several dysregulated genes (e.g., Reln, Phex, and Ltbp2) had been identified in our earlier microarray study of hypertrophic chondrocyte differentiation. Other genes involved in cytokine and chemokine signaling, including Cxcr4 and Ccl2, were identified. Changes in gene expression were also observed in the contralateral knee, validating the sham operation as the appropriate control. CONCLUSION: Our results demonstrate that the animal model mimics gene expression changes seen in human OA, supporting the relevance of newly identified genes and pathways to early human OA. We propose new avenues for OA pathogenesis research and potential targets for novel OA treatments, including cathepsins and cytokine, chemokine, and growth factor signaling pathways, in addition to factors controlling the progression of chondrocyte differentiation. Experiment Overall Design: OA was surgically induced in 5 rats by anterior cruciate ligament transection and partial medial meniscectomy. Sham surgery was performed in 5 additional animals, which were used as controls. Both groups underwent 4 weeks of forced mobilization, 3 times per week. RNA was extracted directly from articular chondrocytes in the OA (operated), contralateral, and sham-operated knees, 28 days post-surgery. Affymetrix GeneChip expression arrays were used to assess genome-wide changes in gene expression.
2009-04-23 | E-GEOD-8077 | biostudies-arrayexpress
Project description:Background: Loss of motion and arthrofibrosis after anterior cruciate ligament reconstruction (ACLR) can be a devastating complication for athletes. The cellular and molecular pathogenesis of arthrofibrosis is poorly understood, limiting prevention and treatment options. Synovial inflammation may contribute to post-ACLR arthrofibrosis. Hypothesis/Purpose: We hypothesized that higher synovial immune cell infiltration and inflammatory/catabolic gene expression patterns at the time of ACLR would correlate with poorer motion-related outcomes. Study Design: Case Series Methods: Patients aged 10-18 undergoing primary ACLR were enrolled in a prospective pilot study, and synovial tissue biopsies were obtained during ACLR. Flow cytometry and single cell RNA-sequencing explored synovial cell types/frequencies and gene expression. Principle component analysis followed by clustering grouped patients into distinct immunophenotypes based on their synovial cell composition. Clinical follow-up with knee range of motion (ROM), need for lysis of adhesions, and patient reported outcome measures were collected and compared between immunophenotypes. Results: Enrolled patients (n = 17) underwent ACLR at a median of 37 days post-injury. Analysis revealed three distinct immunophenotypes. Type 1 comprised patients with the longest time between injury and surgery and the lowest hematopoietic and T cell infiltration. Types 2 and 3 had similar times between injury and surgery, and Type 2 had intermediate while Type 3 had the highest hematopoietic and T cell percentages. Type 3 was associated with worse ROM at 2- and 6-weeks post-op; T cell prevalence and ROM were inversely correlated at those time points. The only patient requiring lysis of adhesions for arthrofibrosis was in Type 3. Conclusion: Synovial immune infiltration after ACL injury shows variability between patients that clusters into three immunophenotypes correlating with early ROM and the risk of arthrofibrosis. T cell recruitment and infiltration was the strongest factor correlated with ROM outcomes and presents an exciting venue for future research on post-ACLR arthrofibrosis.
2024-11-10 | GSE280537 | GEO