Identification of key variants correlated with susceptibility of primary osteoporosis in the Chinese Han group.

BACKGROUND: Primary osteoporosis is a systemic skeletal disease characterized by reduced bone mass and vulnerability to fractures. The genetics of osteoporosis in the Chinese population remain unclear, which hinders the prevention and treatment of osteoporosis in China. This study aimed to explore the susceptibility genes and the roles played by their variants in osteoporosis. METHODS: Blood samples were collected from 45 osteoporosis patients and 30 healthy individuals, and genome-wide association study was performed on array data. The expression levels of the candidate gene in different genotypes were further determined by using quantitative real-time PCR. Moreover, the differentiation capacity of bone marrow mesenchymal stem cells under different genotypes from osteoporosis patients was investigated. RESULTS: The most significant variant rs1891632 located in the upstream (918 bp) region of CRB2, which could down-regulate the expression levels of CRB2 in genotype-tissue expression database and played an essential role in the regulation of osteoblastic and osteoclastic differentiation during skeletal development. Another significant variant rs1061657 located within the 3'UTR region of TBX3 gene. We found that the mRNA levels of TBX3 decreased in the bMSCs of old osteoporosis patients. Interestingly, osteoblast differentiation capacity and TBX3 mRNA levels were similar between the young healthy individuals carrying derived and ancestral allele of rs1061657, whereas the differentiation capacity and TBX3 mRNA levels dramatically declined in elderly patients with osteoporosis. CONCLUSIONS: The variant rs1061657 might affect the osteogenesis of bMSCs in an age-dependent manner and that TBX3 may be a key susceptibility gene for primary osteoporosis. In conclusion, CRB2 and TBX3 may influence the development of osteoporosis; additionally, rs1891632 and rs1061657, as the key variants first reported to be associated with primary osteoporosis, may potentially contribute to predicting the risk of osteoporosis (especially for older individuals) and may serve as therapeutic targets.

Treatment of open and comminuted mid-distal tibial fractures by bilateral external fixation combined with limited-internal fixation.

Open and comminuted mid-distal fractures often result from high-energy trauma, and a concomitant poor blood supply often leads to skin necrosis, infection, and bone union. To circumvent such complications, we used limited-reduction and bilateral-external fixators to treat open and comminuted mid-distal tibial fractures with compromised soft tissue. A retrospective series of 34 patients who had open and comminuted mid-distal tibial fractures and treated by bilateral-external fixators with limited-internal fixation were analyzed. Patients were followed for 10-25 months (mean: 12 months) post-treatment and osseous union was achieved in each case. The average union time was 16.3 weeks. Based on the Johner- Wruhs criteria, the retrospective series consisted of 21 'excellent' cases, 8 'good' cases, 4 'fair' cases, and a 'poor' case. The total percentage of 'excellent' and 'good' cases of fracture recovery was 85.29%. Bilateral-external and limited-internal fixators pro- vided high bone union rate and excellent ankle-joint motion. Hence, it is an appropriate surgical approach for treating open and comminuted mid-distal tibial fractures with compromised soft tissue.

A novel mutation combining with rs66612022 in a Chinese pedigree suggests a new pathogenesis to osteogenesis imperfecta via whole genome sequencing.

Osteogenesis imperfecta (OI) is a rare heritable disease with systemic connective tissue disorder. Most of the patients represent autosomal dominant form of OI, and are usually resulting from the mutations in type I collagen genes. However, the gene mutations reported previously only account for ∼70% of the OI cases. Here, in a Chinese OI family, we examined seven patients and nine normal individuals using the whole genome sequencing and molecular genetic analysis. The mutation of rs66612022 (COL1A2:p.Gly328Ser) related to glycine substitution was found in the seven patients. Moreover, we identified a novel missense mutation (HMMR:p.Glu2Gln). Interestingly, the individuals of this family with both the mutations were suffering from OI, while the others carried one or none of them are normal. The mutations of COL1A2 and HMMR and their combined effect on OI would further expand the genetic spectrum of OI.

No association between HMGB1 polymorphisms and cancer risk: evidence from a meta-analysis.

The aim of the present study was to determine whether High mobility group box 1 (HMGB1) polymorphism was associated with cancer susceptibility. PubMed, Embase, and ISI Web of Science were extensively searched without language restriction. Data were extracted using a standardized data collection sheet after two reviewers scanned studies independently. The association between HMGB1 polymorphism and cancer risks was indicated as odds ratio (OR) along with its related 95% confidence interval (95%CI). Meta-analysis was conducted via RevMan 5.3 software. A total of ten studies comprising 4530 cases and 5167 controls were included in our study. Meta-analysis revealed no statistical association between rs1045411, rs1360485, rs1412125, or rs2249825 polymorphisms in HMGB1 gene and risk of cancer, either did subgroup analysis of rs1045411 stratified by cancer types and ethnic groups. Our results revealed no statistical association between current four polymorphism loci and cancer risks, suggesting that the attempt of applying HMGB1 variants as a therapeutic target or a prognosis predictor might still require a second thought. However, HMGB1 is deemed to play pleiotropic roles in cancers, we strongly call for large-scale studies with high evidence level to uncover the exact relationship between HMGB1 gene variants and cancer progression.

Effect of TERT on the growth of fibrosarcoma via caspase-3, survivin and PKB.

The present study explored the effect of telomerase reverse transcriptase (TERT) on the growth and apoptosis of fibrosarcoma, and investigated the potential molecular signalling pathways underlying its effect. A plasmid was constructed in order to overexpress TERT and siRNA was used to knockdown TERT. The effect of TERT on fibrosarcoma cells in vitro was studied by performing reverse transcription-quantitative PCR and western blotting to determine the expression of p53, survivin, caspase-3, caspase-7 and PKB. Knockdown of TERT suppressed cell growth, decreased fibrosarcoma volume, decreased survivin and PKB expression, and increased caspase-3 expression. The results of the present study suggest that TERT regulates the growth of fibrosarcoma in vitro and in vivo, and that this is associated with the expression of caspase-3 and survivin, in addition to the PKB signalling pathway.

A Novel Brucine Gel Transdermal Delivery System Designed for Anti-Inflammatory and Analgesic Activities.

The seeds of Strychnosnux-vomica L., as a traditional Chinese medicine, have good anti-inflammatory and analgesic activities. However, it usually leads to gastrointestinal irritation and systemic toxicity via oral administration. In the study, it was discovered that a novel gel transdermal delivery system contained brucine, the main effective component extracted from Strychnosnux-vomica. Results showed that the brucine gel system inhibited arthritis symptoms and the proliferation of the synoviocytes in the rat adjuvant arthritis model, which indicated its curative effect for rheumatoid arthritis. Meanwhile, it significantly relieved the xylene-induced ear edema in the mouse ear swelling test, which manifested its anti-inflammatory property. Moreover, the brucine gel eased the pain of paw formalin injection in the formalin test, which demonstrated its analgesic effects. In addition, the brucine significantly inhibited lipopolysaccharide (LPS)-induced Prostaglandin E2 (PGE2) production without affecting the viability of cell in vitro anti-inflammatory test, which proved that its anti-inflammatory and analgesic actions were related to inhibition of prostaglandin synthesis. It is suggested that the brucine gel is a promising vehicle for transdermal delivery on the treatment of inflammatory disease.

Association of chemerin levels in synovial fluid with the severity of knee osteoarthritis.

CONTEXT: Chemerin has been implicated to be correlated with inflammation. OBJECTIVE: This study aims to determine the association of chemerin levels in serum and synovial fluid (SF) with the disease severity of patients with knee Osteoarthritis (OA). METHODS: 124 patients with knee OA and 76 healthy controls were enrolled in this study. RESULTS: Chemerin levels in serum were significant higher with regard to paired SF. Chemerin levles in SF of knee OA patients were correlated with disease severity evaluated by KL grading criteria. CONCLUSION: Chemerin levels may be involved in the pathophysiology of the development and progression of OA.

[Experimental study on osteoking in promoting gene expression of core binding factor alpha 1 in necrotic femoral head of rabbits].

OBJECTIVE: To study the effects of Osteoking in promoting gene expression of core binding factor alpha 1 (cbfalpha 1) in necrotic femoral head of rabbits. METHODS: Rabbit model of femoral head necrosis (FHN) was induced by intravenous injection of lipopolysaccharide (LPS) 10 microg/kg body weight twice with an interval of 24 h and intramuscular injection with methyl prednisone (MPS) 20 mg/kg body weight 3 times. The dynamic changes of cbfalpha 1 gene expression in the femoral head were observed with immunohistochemistry and real-time quantitative PCR. RESULTS: The protein expression of cbfa 1 gene was negative in both model and treatment groups at the 4th week, it turned to weakly positive in the treatment group at the 8th and 12th week but still negative in the model group. The mRNA expression of cbfalpha 1 in the treatment group was 2.87 times that in the model group at the 12th week. There was no significant difference in cbfalpha 1 expression between the normal rabbits with or without Osteoking treatment. CONCLUSION: Osteoking could promote the endogenous cbfalpha 1 expression in the FHN, the effect is better along with the prolonging of the time applied. But it showed no affection on cbfalpha 1 expression in the normal femoral head of rabbits.

Clinical study on effect of Osteoking in preventing postoperational deep venous thrombosis in patients with intertrochanteric fracture.

OBJECTIVE: To evaluate the effect of Osteoking ( masculine(1)i) in preventing postoperational deep venous thrombosis (DVT) in patients with intertrochanteric fracture (ITF). METHODS: With prospective and randomized controlled clinical design adopted, 62 patients with ITF after operation were assigned into 2 groups, the tested group and the control group, Osteoking (25 ml every other day) and Sanchi-dansheng tablets (3 tablets thrice a day) were given orally to them respectively for 10 days. Difference of round length of thighs and shanks between two sides were measured on the 10th day and Doppler ultrasonic examination on the fractured leg was carried out. RESULTS: The occurrence rate of DVT in the tested group was 9.4%, which was lower than that in the control group (30.0%, P < 0.05). All the difference of round lengths, either that of the thigh or the shank, was less in the tested group than that in the control group, showing statistical significance (P < 0.05). CONCLUSION: Osteoking has a satisfactory effect in preventing postoperational DVT in patients with ITF.