Project description:This study aims to compare the genetic profile of fibrotic and non-fibrotic human knee capsular tissue in an effort to identify possible molecular pathways responsible for the development of AF. RNA sequencing (RNA-seq) and bioinformatics were used to define differentially expressed genes (DEGs) and molecular pathways linked to joint stiffening. Gene expression profiling revealed a distinct clustering of each patient group by principal component analysis, hierarchical clustering and similarity matrix analysis. Three prospectively-collected, matched patient cohorts were used to formally describe gene expression signatures of AF patients. The findings define molecular and pathological markers of AF, as well as novel potential targets for pre-diagnosis and pharmacological treatment of AF patients. Overall design: Examination of pTKA (n=4), rTKA-A (n=4) and rTKA-NA (n=4) tissues for molecular markers.
Project description:Total knee arthroplasty (TKA) is a durable and reliable procedure to alleviate pain and improve joint function. However, failures related to flexion instability sometimes occur. The goal of this study was to define biological differences between tissues from patients with and without flexion instability of the knee after TKA. Human knee joint capsule tissues were collected at the time of primary or revision TKAs and analyzed by RT-qPCR and RNA-seq, revealing novel patterns of differential gene expression between the two groups. Interestingly, genes related to collagen production and extracellular matrix (ECM) degradation were higher in samples from patients with flexion instability. Partitioned clustering analyses further emphasized differential gene expression patterns between sample types that may help guide clinical interpretations of this complication. Future efforts to disentangle the effects of physical and biological (e.g., transcriptomic modifications) risk factors will aid in further characterizing and avoiding flexion instability after TKA.
Project description:Objective:To assess the association of GDF-5 rs143383 polymorphism with radiographic defined knee osteoarthritis (OA), a systematic review and meta-analysis was conducted. Methods:A total of 17 relevant case-control studies with 7424 cases and 11,310 controls was collected from several electronic databases up to June 2018. Results:The pooled results showed that GDF-5 rs143383 polymorphism was significantly associated with radiographic defined knee OA in overall and stratified analysis by ethnicity, source of controls and genotyping techniques. Conclusions:The GDF-5 rs143383 polymorphism might be used as a relevant risk estimate for radiographic defined Knee OA.
Project description:Molecular pathology as applied to neoplasia is a rapidly expanding component of the discipline of pathology that uses molecular biology tools in addition to conventional morphologic, immunohistochemical and chemical analyses of abnormalities in tissues and cells to understand the etiology and pathogenesis of tumors, establish their diagnosis, and contribute to prognostication and therapeutic decisions for cancer patient care. Biomarkers are a fundamental component of personalized cancer care, and the discipline of molecular pathology therefore contributes throughout the continuum from biomarker research to use in standard-of-care personalized cancer therapy. This brief review addresses some of the specific roles of molecular pathology in that continuum.
Project description:Objective:To evaluate the association of ESR1 rs2234693 and rs9340799 polymorphisms with radiographic defined knee osteoarthritis (OA), a case-control and meta-analysis was performed. Methods:A total of 25 case-control studies with 7,144 cases and 8,468 controls with were included. Results:There was a significant association between rs2234693 polymorphism and radiographic knee OA under heterozygote model (CT vs. TT: OR?=?1.164, 95% CI 1.053-1.286, p?=?0.003). However, there was no association between rs9340799 and radiographic knee OA. In subgroup analysis by ethnicity, risk estimates were not augmented. Conclusions:Our results showed that the ESR1 rs2234693 polymorphism might be associated with radiographic defined knee OA, but not rs9340799.
Project description:To examine the relationship of knee osteoarthritis (OA) with cardiovascular and metabolic risk factors by obesity status and gender.Data from 1,066 National Health and Nutrition Examination Survey III participants (?60 years of age) was used to examine relationships of osteophytes-defined radiographic knee OA and cardiovascular and metabolic measures. Analyses were considered among obese [body mass index (BMI)?30 kg/m(2)] and non-obese (BMI<30 kg/m(2)) men and women.The prevalence of osteophytes-defined radiographic knee OA was 34%. Leptin levels and homeostatic model assessment-insulin resistance (HOMA-IR), a proxy measure of insulin resistance, were significantly associated with knee OA; those with knee OA had 35% higher HOMA-IR values and 52% higher leptin levels compared to those without knee OA. The magnitude of the association between HOMA-IR and knee OA was strongest among men, regardless of obesity status; odds ratios (ORs) for HOMA-IR were 34% greater among non-obese men (OR=1.18) vs obese women (OR=0.88). Among obese women, a 5-?g/L higher leptin was associated with nearly 30% higher odds of having knee OA (OR=1.28). Among men, ORs for the association of leptin and knee OA were in the opposite direction.Cardiometabolic dysfunction is related to osteophytes-defined radiographic knee OA prevalence and persists within subgroups defined by obesity status and gender. A sex dimorphism in the direction and magnitude of cardiometabolic risk factors with respect to knee OA was described including HOMA-IR being associated with OA prevalence among men while leptin levels were most important among women.
Project description:The prevalence of knee osteoarthritis is traditionally based on radiographic findings, but magnetic resonance imaging is now being used to provide better visualization of bone, cartilage, and soft tissues as well as the patellar compartment. The goal of this study was to estimate the prevalences of knee features defined on magnetic resonance imaging in a population and to relate these abnormalities to knee osteoarthritis severity scores based on radiographic findings, physical functioning, and reported knee pain in middle-aged women.Magnetic resonance images of the knee were evaluated for the location and severity of cartilage defects, bone marrow lesions, osteophytes, subchondral cysts, meniscal and/or ligamentous tears, effusion, and synovitis among 363 middle-aged women (724 knees) from the Michigan Study of Women's Health Across the Nation. These findings were related to Kellgren-Lawrence osteoarthritis severity scores from radiographs, self-reported knee pain, self-reported knee injury, perception of physical functioning, and physical performance measures to assess mobility. Radiographs, physical performance assessment, and interviews were undertaken at the 1996 study baseline and again (with the addition of magnetic resonance imaging assessment) at the follow-up visit during 2007 to 2008.The prevalence of moderate-to-severe knee osteoarthritis changed from 3.7% at the baseline assessment to 26.7% at the follow-up visit eleven years later. Full-thickness cartilage defects of the medial, lateral, and patellofemoral compartments were present in 14.5% (105 knees), 4.6% (thirty-three knees), and 26.2% (190 knees), respectively. Synovitis was identified in 24.7% (179) of the knees, and joint effusions were observed in 70% (507 knees); 21.7% (157) of the knees had complex or macerated meniscal tears. Large osteophytes, marked synovitis, macerated meniscal tears, and full-thickness tibial cartilage defects were associated with increased odds of knee pain and with 30% to 40% slower walking and stair-climbing times.Middle-aged women have a high prevalence of moderate-to-severe knee osteoarthritis corroborated by strong associations with cartilage defects, complex and macerated meniscal tears, osteophytes and synovitis, knee pain, and lower mobility levels.
Project description:Recurrent or chronic activity related knee pain is common in young athletes. Numerous intrinsic conditions affecting the knee can cause such pain. In addition, knee pain can be referred pain from low back, hip or pelvic pathology. The most common cause of knee pain in young athletes is patellofemoral pain syndrome, or more appropriately termed idiopathic anterior knee pain. Although, numerous anatomical and biomechanical factors have been postulated to contribute the knee pain in young athletes, the most common underlying reason is overuse injury. In this paper, we have reviewed selected conditions that case knee pain in athletes, including anterior knee pain syndrome, Osgood-Schlatter disease, Sinding-Larsen-Johanssen syndrome, juvenile osteochondritis dissecans (JOCD), bipartite patella, plica syndrome, and tendonitis around the knee.
Project description:To determine the association of different types of meniscal pathology with knee pain, bone marrow lesion (BML) volume, and end-stage knee osteoarthritis (esKOA).Participants were selected from an ancillary project to the Osteoarthritis Initiative (OAI) who had at least one knee with symptomatic osteoarthritis. Baseline magnetic resonance images (MRI) were evaluated for meniscal pathology using a modified International Society of Arthroscopy, Knee Surgery, and Orthopaedic Sports Medicine (ISAKOS) classification system. We collapsed 10 types of meniscal pathology into five categories: normal, intrameniscal signal, morphological deformity/extrusion (altered meniscal shape and/or extrusion but no apparent substance loss), tear, and maceration. Outcomes included Western Ontario and McMaster Universities osteoarthritis index (WOMAC) knee pain and BML volume at baseline and after 2 years. We defined the prevalence of esKOA based on a validated algorithm. We performed logistic regression and adjusted for age, sex, and body mass index (BMI).The 463 participants (53% male) included in the analysis had mean age 63 (9.2) years, BMI 29.6 (4.6) kg/m2, and 71% had Kellgren-Lawrence grade ?2. Morphological deformity/extrusion and maceration, but no other types of meniscal pathology, were associated with BML volume (morphological deformity/extrusion odds ratio [OR] = 2.47, 95% CI: 1.49, 4.09, maceration OR = 5.85, 95% CI: 3.40, 10.06) and change in BML volume (morphological deformity/extrusion OR = 2.17, 95% CI: 1.37, 3.45, maceration OR = 3.12, 95% CI: 1.87, 5.19). Only maceration was associated with baseline WOMAC knee pain (OR = 2.82, 95% CI: 1.79, 4.43) and prevalence of esKOA (OR = 7.53, 95% CI: 4.25, 13.31).Based on MRI, morphologic deformity/extrusion and maceration rather than intrameniscal signal or tear were associated with osteoarthritis severity and progression, which highlights the importance of differentiating distinct types of meniscal pathology.