Huajian Teng

Association of Single Nucleotide Polymorphisms in Estrogen Receptor Alpha Gene with Susceptibility to Knee Osteoarthritis: A Case-Control Study in a Chinese Han Population

Osteoarthritis (OA) is the most prevalent form of arthritis and its multifactorial nature has been increasingly recognized. Genetic factors play an important role in OA etiology and estrogen receptor alpha (ESR1) gene polymorphisms may be involved. This study tried to explore whether the ESR1 gene single nucleotide polymorphisms (SNPs) were associated with primary knee OA in the Chinese Han population. Two SNPs, rs2234693 and rs9340799, were genotyped in 469 cases and 522 controls. Rs2234693 was associated with knee OA in the dominant genetic model (TT + TC versus CC) (P = 0.025) and a higher T allele frequency existed (P = 0.047) among females. The combined genotype (TT + TC) (P = 0.025) and T allele (P = 0.016) were related with mild knee OA only. For rs9340799, A allele was associated with knee OA in all subjects (P = 0.031) and females (P = 0.046). Statistical differences were detected in the dominant genetic model (AA + AG versus GG) among females (P = 0.030). The combined genotype (AA + AG) (P = 0.036) and A allele (P = 0.039) were merely correlated with mild knee OA. ESR1 gene is considerably associated with knee OA etiology in the Chinese Han population.

Association of a single nucleotide polymorphism in HOXB9 with developmental dysplasia of the hip: a case-control study.

Developmental dysplasia of the hip (DDH) is one of the most common skeletal disorders. It comprises a spectrum of abnormalities, including shallow acetabulum and decreased coverage of the femoral head. Genetic component plays a considerable role in the aetiology of DDH. HOXB9 may be involved in the aetiology and pathogenesis of DDH, as it plays an important role in the development of the limbs. Our objective was to evaluate whether single nucleotide polymorphisms (SNPs) of HOXB9 (rs2303486 and rs8844) were associated with DDH in Chinese population. The HOXB9 tag SNPs were genotyped in 460 DDH cases and 562 control subjects by Taqman assay, and their association was examined. rs8844 was not associated with DDH. rs2303486 was associated with DDH in the dominant genetic model (p = 0.037; odds ratio (OR) = 1.32; 95% confidence interval (CI) = 1.02–1.71). After stratification by sex, significant association of the dominant genetic model still existed in the female subjects (p = 0.015; OR = 1.46; 95% CI = 1.08–1.98), but not in the male subjects. After stratification by severity, we discovered an association with hip dislocation in the dominant model (p = 0.042; OR = 1.35; 95% CI = 1.01–1.80), but not with subluxation or instability. HOXB9 is associated with DDH in Chinese.

In vivo repair of full-thickness cartilage defect with human iPSC-derived mesenchymal progenitor cells in a rabbit model

Cell-based tissue engineering has the potential to restore cartilage defects. Induced pluripotent stem cells (iPSCs) are regarded as an alternative cell source in regenerative medicine. The purpose of the present study was to evaluate the use of mesenchymal stem cells (MSCs) derived from human iPSCs (hiPSCs) for the regeneration of cartilage defects in a rabbit model. Cartilage defects were made in the patellar grooves of New Zealand white rabbits. The rabbits were then divided into three groups according to implantation: Control group, scaffold implantation group and scaffold/hiPSCs-MSCs (experimental) group. MSCs were generated from hiPSCs via a step of embryoid body formation. Following flow cytological analysis, the hiPSCs-MSCs were plated onto poly(lactic-co-glycolide) and then transplanted into the cartilage defects in the experimental group. Six rabbits from each group were sacrificed at each time point. The outcome was assessed macroscopically and histologically at 3 and 6 weeks post-surgery. At 3 and 6 weeks, the experimental group showed more cartilage defect filling compared with the control and scaffold implantation groups. At 3 weeks, the experimental group showed much more repair tissue in the cartilage defect, although no cartilage-like tissue was observed. At 6 weeks, cartilage-like tissue was observed in the experimental group but not in the control or scaffold implantation groups. No teratoma formation was observed in any of the groups. The results indicate that iPSCs have the potential to repair cartilage defects in vivo. Therefore, iPSCs could be a new cell source for cartilage defect repair.

Deep Vein Thrombosis After Total Hip Arthroplasty and Total Knee Arthroplasty in Patients With Previous Ischemic Stroke

The present study evaluated the prevalence and therapy of deep vein thrombosis (DVT) after total hip arthroplasty (THA) and total knee arthroplasty (TKA) in 57 patients with previous ischemic stroke. Postoperative anticoagulants were used for DVT prophylaxis, and batroxobin and prolonged anticoagulants were used for thrombolysis in DVT subjects. The incidence of DVT after THA and TKA in patients with previous ischemic stroke was 16.2% and 20%, respectively. No bleeding complications were observed and no new ischemic stroke occurred during the following 3 months. The prevalence DVT after THA and TKA in patients with previous ischemic stroke was not specific, and the treatment of DVT with batroxobin and anticoagulants was effective and safe.

AMPK deficiency in chondrocytes accelerated the progression of instability-induced and ageing-associated osteoarthritis in adult mice

Osteoarthritis (OA) is a progressive degenerative disease of the joints that is associated with both joint injury and ageing. Here, we investigated the role of the energy sensor AMP-activated protein kinase (AMPK) in maintaining a healthy state of articular cartilage and in OA development. Using cartilage-specific, tamoxifen-inducible AMPKα1 conditional knockout (AMPKα1 cKO), AMPKα2 conditional knockout (AMPKα2 cKO) and AMPKα1α2 conditional double knockout (AMPKα cDKO) mice, we found that compared with wild-type (WT) littermates, mutant mice displayed accelerated severity of surgically induced OA, especially AMPKα cDKO mice. Furthermore, male but not female AMPKα cDKO mice exhibited severely spontaneous ageing-associated OA lesions at 12 months of age. The chondrocytes isolated from AMPKα cDKO mice resulted in an enhanced interleukin-1β (IL-1β)-stimulated catabolic response. In addition, upregulated expression of matrix metalloproteinase-3 (MMP-3), MMP-13 and phospho-nuclear factor-κB (phospho-NF-κB) p65 and increased levels of apoptotic markers were detected in the cartilage of AMPKα cDKO mice compared with their WT littermates in vivo. Thus, our findings suggest that AMPK activity in chondrocytes is important in maintaining joint homeostasis and OA development.

Novel WISP3 mutations causing progressive pseudorheumatoid dysplasia in two Chinese families

Progressive pseudorheumatoid dysplasia (PPD) is a rare disease caused by mutations in the gene for Wnt1-inducible signaling pathway protein 3 (WISP3). Here, we report the clinical and radiographic manifestations of two Chinese PPD patients. We performed whole-exome sequencing for one patient and sequenced the WISP3 for the other. Three WISP3 mutations (c.396T>G, c.721T>G and c.679dup) were identified; the two missense mutations were novel. Our study expanded the WISP3 mutation spectrum.

A Common Variant Of Ubiquinol-Cytochrome c Reductase Complex Is Associated with DDH

Purpose Genetic basis of Developmental dysplasia of the hip (DDH) remains largely unknown. To find new susceptibility genes for DDH, we carried out a genome-wide association study (GWAS) for DDH. Methods We enrolled 386 radiology confirmed DDH patients and 558 healthy controls (Set A) to conduct a genome-wide association study (GWAS). Quality-control was conducted at both the sample and single nucleotide polymorphism (SNP) levels. We then conducted a subsequent case-control study to replicate the association between a promising loci, rs6060373 in UQCC gene and DDH in an independent set of 755 cases and 944 controls (set B). Results In the DDH GWAS discovering stage, 51 SNPs showed significance of less than 10-4, and another 577 SNPs showed significance of less than 10-3. In UQCC, all the 12 genotyped SNPs showed as promising risk loci. Genotyping of rs6060373 in set A showed the minor allele A as a promising risk allele (p = 4.82*10-7). In set A, the odds ratio of allele A was 1.77. Genotyping of rs6060373 in Set B produced another significant result (p = 0.0338) with an odds ratio of 1.18 for risk allele A. Combining set A and set B, we identified a total p value of 3.63*10-6 with the odds ratio of 1.35 (1.19–1.53) for allele A. Conclusion Our study demonstrates common variants of UQCC, specifically rs6060373, are associated with DDH in Han Chinese population.

Postoperative plasma D-dimer value for predicting deep venous thrombosis following hip arthroplasty with nadroparin prophylaxis

The aim of the study was to assess the value of D-dimer as an event predicitor for deep vein thrombosis (DVT) in patients given low molecular weight heparin (LMWH) after total hip arthroplasty (THA). Plasma D-dimer levels were obtained preoperatively and at days 1, 3, and 7 postoperatively in 83 consecutive patients undergoing THA treated with nadroparin prophylaxis plus intermittent pneumatic compression. Unilateral ascending venography was performed at postoperative day 7 or 8. There was a significant difference between the D-dimer levels in the DVT group (28 patients) and non-DVT group (55 patients) on each day (P<0.01). ROC analysis showed the AUC on postoperative days 1, 3 and 7 was 0.706, 0.712 and 0.772 respectively. The D-dimer concentration on postoperative day 1, day 3 or day 7 is of moderate predicting value of DVT in patients undergoing THA, treated with nadroparin prophylaxis plus intermittent pneumatic compression.

Serum levels of the bone turnover markers dickkopf-1, osteoprotegerin, and TNF-α in knee osteoarthritis patients

Knee osteoarthritis (KOA) is a common degenerative joint disease causing pain, stiffness, reduced motion, swelling, crepitus, and disability. Several inflammatory markers and cartilage degradation products can be used as biomarkers in OA. The key factors of bone metabolism in normal joint bone, dickkopf-1 (DKK1) and osteoprotegerin (OPG), interact with Wnt signaling pathway, balancing between bone absorption and bone reconstruction. TNF-α is a key inducer of DKK-1, which belongs to the family of proteins involved in joint remodeling. The present study compared the serum levels of DKK1, TNF-α, and OPG in patients with KOA and healthy controls to analyze the interrelationship and the severity of joint destruction. One hundred forty-eight patients with KOA and 101 healthy controls were enrolled in this study. Anteroposterior knee radiographs determined the severity of the disease in the affected knee. The radiographic grading of KOA was performed by the Kellgren–Lawrence criteria. Serum levels of DKK-1, TNF-α, and OPG were estimated using the multiplex particle-based flow cytometry. Higher serum levels of OPG and TNF-α were observed in KOA than the controls; KOA patients showed a lower serum level of DKK-1, whereas the serum levels of DKK1 correlated with the progression of KOA. The serum levels of TNF-α, OPG, and DKK-1 correlated with incident KOA. In the ROC curve analysis, DKK1 levels showed 78.6% sensitivity and 40% specificity, TNF-α levels showed 74.1% sensitivity and 76.0% specificity, and OPG showed 88.1% sensitivity and 81% specificity in predicting severe KOA. In the univariate and multivariate analyses, TNF-α and OPG emerged as independent predictors of severe KOA. This study, for the first time, combined TNF-α, DKK1, and OPG as valuable biological markers in predicting the severity of KOA radiographically in the clinic. This study also supported the inflammation-induced DKK1 and OPG in OA pathogenesis.

A Replication Study for the Association of rs726252 in PAPPA2 with Developmental Dysplasia of the Hip in Chinese Han Population

Developmental dysplasia of the hip (DDH) is a common developmental hip disorder, which ranges from mild acetabulum malformation to irreducible hip dislocation. A previous study suggested a significant association of pregnancy-associated plasma protein-A2 (PAPPA2) with DDH susceptibility in Chinese Han population. But with the consideration of the sample size, the association was still debatable. To confirm the association of the reported single nucleotide polymorphism (SNP) in PAPPA2, rs726252 with DDH, we conducted a case-control study in a larger number of subjects. We genotyped rs726252 in 697 DDH subjects and 707 control subjects by TaqMan assay. The association between this SNP and DDH was evaluated statistically. No significant difference was found in any comparison of genotype distribution nor allele frequency between cases and controls. Our replication study indicated that the association between rs726252 and DDH in Chinese Han population was debatable. The association between PAPPA2 and DDH should be evaluated by additional studies.