Project description:Aims: Developmental dysplasia of the hip (DDH) is a complex musculoskeletal disease that occurs mostly in children. This study aimed to investigate the molecular changes in the hip joint capsule of patients with DDH. Results: More than one thousand genes were differentially expressed in hip joint capsules between healthy controls and DDH. Both gene ontology (GO) and Kyoto encyclopedia of genes and genome (KEGG) analyses revealed that extracellular matrix (ECM) modifications, muscle system processes, and cell proliferation were markedly influenced by the differentially expressed genes. Conclusion: DDH is associated with the loss of collagen fibers and fibroblasts, which may cause loose joint capsule formation. However, the degree of differentiation of fibroblasts to myofibroblasts needs further studies.
Project description:Developmental dysplasia of the hip (DDH) is one of the significant risk factors for hip osteoarthritis. In order to investigate the factors that induce early articular cartilage degeneration of the hip joints that are exposed to reduced dynamic loads arising from hip dislocation , we created rodent models of hip dislocation by swaddling. Notably, expression of periostin (Postn) was increased in the acetabular articular cartilage of the DDH models; Postn was a candidate gene associated with early articular cartilage degeneration. We showed that early articular cartilage degeneration was suppressed in Postn-/- DDH mice. Furthermore, a microgravity environment induced the expression of Postn in chondrocytes through STAT3 signaling. Postn induced catabolic factors, interleukin-6 and matrix metalloproteinase 3, in articular chondrocytes through integrin-nuclear factor κB signaling. Additionally, interleukin-6 stimulated Postn expression through STAT3 signaling. Thus, Postn plays a critical role in early articular cartilage degeneration associated with hip dislocation.
Project description:The intent of the experiment was to identify genes that were differentially expressed between dogs affected with anterior cruciate ligament (ACL) rupture and breed-matched controls. Anterior cruciate ligament and knee synovial tissue biopsies were collected from 4 ACL rupture affected cases and 4 unaffected control dogs. Cases and controls were matched as closely as possible based on breed, sex, neutered status, age, and weight. Medications that the dogs were taking at the time of sample collection were also considered. We prioritized sample size and quality above all other variables, therefore, two matched pairs of Golden Retrievers were chosen with two matched pairs of Labrador Retrievers for this analysis. Tissues from cases were collected during knee stabilization surgery. Tissues from unaffected control dogs were collected from dogs undergoing pelvic limb amputation or euthanasia for reasons unrelated to this study. Illumina TruSeq RNA libraries were constructed and 150bp paired-end sequencing was performed using the Illumina Hi-Seq 2500 platform. Table 1. Breed, sex, age, and weight of matched case and control pairs chosen for RNA sequencing analysis Cases Matched Controls Breed Sex Age (yr) Weight (kg) Breed Sex Age (yr) Weight (kg) GR1 CM 8.8 30.5 GR2 CM 14.9 N/A GR3 CM 5.6 44.0 GR4 CM 3.9 34.0 LR1 CM 9.7 36.0 LR2 CM 12.7 28.5 LR3 CM 13.3 36.0 LR4 CM 13.5 35.0 GR = Golden Retriever. LR = Labrador Retriever. CM= castrated male. Weight at the time of death was not available for one dog.
Project description:Developmental dysplasia of the hip (DDH) is a complex and multifactorial disease with an unclear pathogenesis, and the non-coding RNAs have been found important effect in many diseases. However, their contributions to the pathogenesis of DDH are not well-established. Growth of the acetabular cartilage mainly depends on the regulation of chondrocytes in proliferative zone. Here, we report on some new regulatory mechanisms of gene expression underlying the development of DDH by transcriptome profiling of proliferative zone microdissected from the acetabular cartilage. These results provide original insight into the roles of non-coding RNAs in DDH and provide a valuable resource for further analyses of molecular mechanisms and signaling networks.
