Osteoporosis (OP) is a metabolic bone disease, characterized by a decrease in bone mineral density (BMD). However, the research of regulatory variants has been limited for BMD. In this study, we aimed to explore novel regulatory genetic variants associated with BMD. We conducted an integrative analysis of BMD genome-wide association study (GWAS) and regulatory single nucleotide polymorphism (rSNP) annotation information. Firstly, the discovery GWAS dataset and replication GWAS dataset were integrated with rSNP annotation database to obtain BMD associated SNP regulatory elements and SNP regulatory element-target gene (E-G) pairs, respectively. Then, the common genes were further subjected to HumanNet v2 to explore the biological effects.Aims
Methods
The aim of this study was to explore the genetic correlation and causal relationship between blood plasma proteins and rheumatoid arthritis (RA). Based on the genome-wide association studies (GWAS) summary statistics of RA from European descent and the GWAS summary datasets of 3,622 plasma proteins, we explored the relationship between RA and plasma proteins from three aspects. First, linkage disequilibrium score regression (LD score regression) was applied to detect the genetic correlation between RA and plasma proteins. Mendelian randomization (MR) analysis was then used to evaluate the causal association between RA and plasma proteins. Finally, GEO2R was used to screen the differentially expressed genes (DEGs) between patients with RA and healthy controls.Aims
Methods
Despite the interest in the association of gut microbiota with bone health, limited population-based studies of gut microbiota and bone mineral density (BMD) have been made. Our aim is to explore the possible association between gut microbiota and BMD. A total of 3,321 independent loci of gut microbiota were used to calculate the individual polygenic risk score (PRS) for 114 gut microbiota-related traits. The individual genotype data were obtained from UK Biobank cohort. Linear regressions were then conducted to evaluate the possible association of gut microbiota with L1-L4 BMD (n = 4,070), total BMD (n = 4,056), and femur total BMD (n = 4,054), respectively. PLINK 2.0 was used to detect the single-nucleotide polymorphism (SNP) × gut microbiota interaction effect on the risks of L1-L4 BMD, total BMD, and femur total BMD, respectively.Aims
Methods
Osteosarcoma (OSA) is a rare, but disproportionately lethal cancer that predominantly affects children. Sadly, discovery of new therapies for OSA has largely been unsuccessful in the past 30 years; there is an urgent need to identify new treatments for OSA. Pet dogs with naturally-occurring OSA represent a unique comparative “model” to discover new treatments for OSA. Unlike humans, in which fewer than 1,000 cases of OSA occur each year, there are nearly 50,000 new cases each year of OSA in dogs. In addition, dogs have an intact immune system, a shared environment with humans, and more rapid progression of disease. Together these factors make dogs an important comparative model for new therapies for OSA. The purpose of this study was: 1) to validate this mouse-dog-human pipeline for drug discovery and 2) to validate CRM1 as a novel target for ostesoarcoma treatment. We developed patient-derived cell lines and xenografts of OSA from both dogs and humans and applied these models to identify new therapies for OSA using high-throughput drug screens in vitro followed by in vivo validation. Whole exome sequencing was performed on the patient-derived models and original tumors to identify potential driver mutations. A high-throughput screen in both dog and human OSA identified CRM1 inhibitors as effective at killing dog and human OSA patient-derived cell lines in vitro. In vivo, CRM1 inhibition led to significant tumor growth inhibition in patient-derived xenografts from dogs and humans. Western blotting demonstrated increased levels of CRM1 protein expression across nine different dog and human OSA cell lines compared to non-transformed human osteoblasts. CRM1 upregulation in OSA cells was further verified by immunofluorescence staining. Increased CRM1 expression was prognostic for poorer metastasis-free survival and poorer overall survival. Our cross-species personalized medicine pipeline identified CRM1 as a potential therapeutic target to treat OSA in both dogs and humans. Future studies are focused on testing CRM1 inhibitors in canine clinical trials.
Kashin-Beck disease (KBD) is a kind of chronic osteochondropathy, thought to be caused by environmental risk factors such as T-2 toxin. However, the exact aetiology of KBD remains unclear. In this study, we explored the functional relevance and biological mechanism of cartilage oligosaccharide matrix protein (COMP) in the articular cartilage damage of KBD. The articular cartilage specimens were collected from five KBD patients and five control subjects for cell culture. The messenger RNA (mRNA) and protein expression levels were detected by quantitative reverse transcription PCR (qRT-PCR) and western blot. The survival rate of C28/I2 chondrocyte cell line was detected by MTT assay after T-2 toxin intervention. The cell viability and mRNA expression levels of apoptosis related genes between Aims
Methods
Osteoarthritis (OA) is the most prevalent joint disease. However, the specific and definitive genetic mechanisms of OA are still unclear. Tissue-related transcriptome-wide association studies (TWAS) of hip OA and knee OA were performed utilizing the genome-wide association study (GWAS) data of hip OA and knee OA (including 2,396 hospital-diagnosed hip OA patients versus 9,593 controls, and 4,462 hospital-diagnosed knee OA patients versus 17,885 controls) and gene expression reference to skeletal muscle and blood. The OA-associated genes identified by TWAS were further compared with the differentially expressed genes detected by the messenger RNA (mRNA) expression profiles of hip OA and knee OA. Functional enrichment and annotation analysis of identified genes was performed by the DAVID and FUMAGWAS tools.Aims
Methods
Shoulder instability is a common cause of morbidity amongst Professional Rugby Union players. This study explores whether the risk of shoulder dislocation is associated with innate shoulder laxity. A randomised controlled study was completed in which all the Premiership Rugby Clubs in England were visited in 2006. 169 professional rugby players (mean age 25.1 years) with no history of instability in either shoulder were assessed and 46 injured players with one shoulder with a history of Bankart lesion or dislocation (mean age 27.5 years) also took part in this study. Shoulder laxity was measured by dynamic ultrasound. Anterior, posterior and inferior translations were measured in both shoulders for healthy players and the uninjured shoulder only for injured players.Objective
Methods
Shoulder instability is a common cause of morbidity amongst Professional Rugby Union players. This study explores whether the risk of shoulder dislocation is associated with innate shoulder laxity. A prospective, randomised controlled study was completed in which all the Premiership Rugby Clubs in England were visited. 169 professional rugby players with no history of instability in either shoulder and 46 players with one shoulder with clinical instability symptoms were assessed. Shoulder laxity was measured by clinical evaluation, questionnaires and ultrasound. Anterior, posterior and inferior translation was measured in both shoulders for healthy players and the uninjured shoulder only for injured players. The results showed there was no significant difference between the left (anterior: mean 2.92 +/− 1.15 mm; posterior: mean 5.10 +/− 1.75 mm; inferior: mean 3.08 +/− 1.00 mm) and right (anterior: mean 3.07 +/− 1.14 mm; posterior: mean 4.87 +/− 1.61 mm; inferior: mean 2.91 +/− 0.99 mm) shoulders in healthy players (P >
0.05). The comparison between healthy shoulders (anterior: mean 3.00 +/− 1.15 mm; posterior: mean 4.99 +/− 1.68 mm; inferior: mean 3.00 +/− 1.00 mm) from healthy players and the uninjured shoulder (anterior: mean 4.16 +/− 1.70 mm; posterior: mean 6.16 +/− 3.04 mm; inferior: mean 3.42 +/− 1.18 mm) from injured players identified that players with unstable shoulders have a significantly higher shoulder translation in their normal shoulder than healthy players (P <
0.05). This is the first study looking at laxity and the risk of shoulder dislocations in sportsmen involved in a high contact sport. These results support the hypothesis that rugby players with “lax” shoulders are more likely to sustain a dislocation or subluxation injury to one of these lax shoulders in their sport.
