Project description:The evolution of human bipedalism exposed the knee to unique biomechanical challenges, requiring changes in knee anatomy giving rise to the modern-day configuration. In order to better understand the relationship between derived knee morphology and the genetic factors associated with osteoarthritis risk, we performed epigenetic profiling of murine forelimb/hindlimb growth plates to identify regulatory elements shaping formation of specific knee structures, identifying signals of ancient positive selection upon which more recent genetic drift overlaps risk-associated loci. Our functional analyses of an osteoarthritis-risk variant within a reproducibly-associated locus establishes a novel model for studying this degenerative disease.
Project description:A novel-cell free bioactive formulation (BIOF2), US Patent No. 9669074B2, for arthrosic chondrocytes has been recently developed and proved as effective for treating severe knee osteoarthritis, we evaluated transcriptome changes in BIOF2-treated synovial fluid cells, isolated from patients with severe knee osteoarthritis to establish BIOF2 mechanism of action.
Project description:Objective: we aimed to identify circulating microRNAs associated with fast-progressing knee osteoarthritis (OA) as compared to slow-progressing knee OA and non-progressing knee OA using sujects from the Osteoarthritis Initiative (OAI) cohort. MicroRNA libraries were prepared from plasma using the QIAseq miRNA Library Kit (QIAGEN) and sequenced on the Illumina NextSeq550 using a single-end 75-base read protocol to an average depth of 11.6 ± 2.6 SD million reads per sample.
Project description:We have compared synovial biopsies from ankylosing spondylitis and undifferentiated spondylitis patients with healthy controls and osteoarthritis patients Objective: In spondylarthropies, whole-genome gene expression profiling studies have been limited to peripheral blood to date. By undertaking a study in knee synovial biopsies from spondylarthropy (SpA) and ankylosing spondylitis (AS) patients we aimed to identified joint-specific candidate genes and pathways. These pathways may mediate systemic inflammation driven joint damaging processes and more specifically, the osteoproliferation that is characteristic of these conditions. Methods: RNA was extracted from six seronegative SpA, two AS, three osteoarthritis (OA) and four normal control knee synovial biopsies. Whole genome expression profiling was undertaken using the Illumina DASL system, which assays 24000 cDNA probes. Differentially expressed candidate genes were then validated using quantitative PCR and immunohistochemistry. Results: 416 differentially expressed genes were identified that clearly delineated between AS/SpA and control groups. Pathway analysis showed altered gene-expression in oxidoreductase activity, osteoblast activity, B-cell associated, matrix catabolic, and metabolic pathways. The inflammatory mediator, MMP3, was strongly upregulated in AS/SpA samples and the Wnt pathway inhibitors DKK3 and Kremen1 were downregulated. Conclusion: Pathways mediating both systemic inflammation as well as local tissue changes were identified. This suggests initial systemic inflammation in spondylarthropies transfers to and persists in the local joint environment, subsequently mediating changes in genes directly involved in the destructive tissue remodelling. Fifteen knee synovial biopsy tissue samples consisting of six seronegative spondyloarthropy (SpA), two ankylosing spondylitis (AS), three osteoarthritis (OA) and four normal control biopsies were obtained from the Synovial Tissue Bank at the Repatriation General Hospital in Adelaide, South Australia with the appropriate ethical approval (Supplementary Table 1). All patients provided informed written consent.
Project description:<p>The Osteoarthritis Initiative (OAI) is a publicly and privately funded prospective longitudinal cohort with a primary objective of identifying risk factors for incidence and progression of tibiofemoral knee OA. The OAI utilized a focused population-based recruitment to enroll 4,674 men and women between the ages of 45-79 years who either had radiographic symptomatic knee OA or who were without radiographic symptomatic OA in both knees but were considered high risk for OA because they had two or more known risk factors for knee OA. Subjects were recruited into the baseline phase of the OAI at multiple sites throughout the US between 2004 and 2006. All subjects were invited back for follow-up examinations to assess incidence or progression of OA annually, for up to 5 years.</p> <p>Phenotype data from the baseline and follow-up examinations are available for public access from the Osteoarthritis Initiative (OAI) database at <a href="http://www.oai.ucsf.edu/">http://www.oai.ucsf.edu/</a>. </p> <p>The Genetic Components of Knee Osteoarthritis (GeCKO) Study was initiated in 2009 as a genetic ancillary study to perform a genome-wide association study to identify genetic variants associated with radiographic osteoarthritis. This study included 4,482 individuals participating in the parent OAI study. Following sample cleaning (e.g., removal of duplicates, sex mismatches, poor sample quality, etc.), the final sample set included 4,129 individuals.</p>
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.
Project description:Certain mouse strains have the ability to heal both ear wounds and knee articular cartilage injuries. A positive genetic correlation between cartilage healing and protection from osteoarthritis exists, which suggests that a common core of genes may operate in healing process. Here, we analyzed knee joint tissues from healer and non-healer mice and found that four genes were common to both ear wound and knee cartilage healing. Specific sequence differences between haler and non-healer parental strains were identified as potential causal polymorphisms. We suggest a common molecular and genetic basis of tissue healing.