Yanyan Bian

Glucocorticoid Receptor and Sequential P53 Activation by Dexamethasone Mediates Apoptosis and Cell Cycle Arrest of Osteoblastic MC3T3-E1 Cells

Glucocorticoids play a pivotal role in the proliferation of osteoblasts, but the underlying mechanism has not been successfully elucidated. In this report, we have investigated the molecular mechanism which elucidates the inhibitory effects of dexamethasone on murine osteoblastic MC3T3-E1 cells. It was found that the inhibitory effects were largely attributed to apoptosis and G1 phase arrest. Both the cell cycle arrest and apoptosis were dependent on glucocorticoid receptor (GR), as they were abolished by GR blocker RU486 pre-treatment and GR interference. G1 phase arrest and apoptosis were accompanied with a p53-dependent up-regulation of p21 and pro-apoptotic genes NOXA and PUMA. We also proved that dexamethasone can’t induce apoptosis and cell cycle arrest when p53 was inhibited by p53 RNA interference. These data demonstrate that proliferation of MC3T3-E1 cell was significantly and directly inhibited by dexamethasone treatment via aberrant GR activation and subsequently P53 activation.

Cemented versus uncemented hemiarthroplasty for femoral neck fractures in elderly patients: a meta-analysis.

Objective Controversy still exists regarding using cemented or uncemented hemiarthroplasty for femoral neck fractures in elderly patients. The aim of this study is to compare the effectiveness and safety of the two surgical techniques in femoral neck fracture patients over 70 years old. Methods We searched PUBMED, EMBASE, Cochrane Library, CNKI and VIP Database from inception to December 2012 for relevant randomized controlled trials (RCTs). Outcomes of interest include postoperative hip function, residue pain, complication rates, mortality, reoperation rate, operation time and intraoperative blood loss. Odds ratios (OR) and weighted mean differences (WMD) from each trial were pooled using random-effects model or fixed-effects model given on the heterogeneity of the included studies. Results 7 RCTs involving 1,125 patients (1,125 hips) were eligible for meta-analysis. Our results demonstrate that cemented hemiarthroplasty is associated with better postoperative hip function (OR = 0.48, 95% CI, 0.31–0.76; P = 0.002), lower residual pain (OR = 0.43, 95%CI, 0.29–0.64; P<0.0001), less implant-related complications (OR = 0.15, 95%CI, 0.09–0.26; P<0.00001) and longer operation time (WMD = 7.43 min, 95% CI, 5.37–9.49 min; P<0.00001). No significant difference was observed between the two groups in mortality, cardiovascular and cerebrovascular complications, local complications, general complications, reoperation rate and intraoperative blood loss. Conclusions Compared with uncemented hemiarthroplasty, the existing evidence indicates that cemented hemiarthroplasty can achieve better hip function, lower residual pain and less implant-related complications with no increased risk of mortality, cardiovascular and cerebrovascular complications, general complications, local complications and reoperation rate in treating elderly patients with femoral neck fractures.

Posterior Cruciate Ligament Retention versus Posterior Stabilization for Total Knee Arthroplasty: A Meta-Analysis

Introduction Although being debated for many years, the superiority of posterior cruciate-retaining (CR) total knee arthroplasty (TKA) and posterior-stabilized (PS) TKA remains controversial. We compare the knee scores, post-operative knee range of motion (ROM), radiological outcomes about knee kinematic and complications between CR TKA and PS TKA. Methods Literature published up to August 2015 was searched in PubMed, Embase and Cochrane databases, and meta-analysis was performed using the software, Review Manager version 5.3. Results Totally 14 random control trials (RCTs) on this topic were included for the analysis, which showed that PS and CR TKA had no significant difference in Knee Society knee Score (KSS), pain score (KSPS), Hospital for Special Surgery score (HSS), kinematic characteristics including postoperative component alignment, tibial posterior slope and joint line, and complication rate. However, PS TKA is superior to CR TKA regarding post-operative knee range of motion (ROM) [Random Effect model (RE), Mean Difference (MD) = -7.07, 95% Confidential Interval (CI) -10.50 to -3.65, p<0.0001], improvement of ROM (Fixed Effect model (FE), MD = -5.66, 95% CI -10.79 to -0.53, p = 0.03) and femoral-tibial angle [FE, MD = 0.85, 95% CI 0.46 to 1.25, p<0.0001]. Conclusions There are no clinically relevant differences between CR and PS TKA in terms of clinical, functional, radiological outcome, and complications, while PS TKA is superior to CR TKA in respects of ROM, while whether this superiority matters or not in clinical practice still needs further investigation and longer follow-up.

Patellar Denervation in Total Knee Arthroplasty Without Patellar Resurfacing and Postoperative Anterior Knee Pain: A Meta-Analysis of Randomized Controlled Trials

The aim of this meta-analysis was to investigate whether patellar denervation with electrocautery (PD) after total knee arthroplasty (TKA) could reduce the postoperative anterior knee pain (AKP). Five randomized controlled trials (RCTs) with 572 patients and 657 knees were eligible for this meta-analysis. Our results showed that PD was associated with less AKP, lower visual analogue scale (VAS), higher patellar scores and better knee function compared with no patellar denervation (NPD). Complications did not differ significantly between the two groups. The existing evidence indicates that PD may be a better approach, as it improves both anterior knee pain and knee function after TKA. Future multi-center randomized controlled studies with large sample sizes are required to verify the current findings.

Pathogenesis of glucocorticoid-induced avascular necrosis: A microarray analysis of gene expression in vitro

Avascular necrosis of the femoral head (ANFH) occurs following exposure to corticosteroids, and the proliferative capacity of the mesenchymal stem cells (MSCs) belonging to ANFH was reduced. The previous studies indicate that microRNA (miRNA) has an important regulatory role during proliferation and osteogenic differentiation of MSCs. Therefore, MSCs were obtained from healthy adults, and were cultured and osteogenically-induced by different dexamethasone concentrations. The proliferation and osteogenic differentiation capacities were examined through observing cellular morphology, alkaline phosphatase and alizarin red; miRNA expression was investigated using an miRNA gene chip and miRNA of differential expressions were retrieved through a database to analyze its regulatory effect. Dexamethasone at a concentration of 10−7 mol/l induced the proliferation and osteogenic differentiation of MSCs and resulted in evident miRNA expression profile changes. In total, 11 miRNAs were upregulated at 10−7 mol/l while 6 were downregulated, and partial miRNA was identified to participate in the regulation of cell proliferation and cell apoptosis, MSC osteogenic differentiation, lipid metabolism and other processes.

Influence of Nano-HA Coated Bone Collagen to Acrylic (Polymethylmethacrylate) Bone Cement on Mechanical Properties and Bioactivity.

Objective This research investigated the mechanical properties and bioactivity of polymethylmethacrylate (PMMA) bone cement after addition of the nano-hydroxyapatite(HA) coated bone collagen (mineralized collagen, MC). Materials & Methods The MC in different proportions were added to the PMMA bone cement to detect the compressive strength, compression modulus, coagulation properties and biosafety. The MC-PMMA was embedded into rabbits and co-cultured with MG 63 cells to exam bone tissue compatibility and gene expression of osteogenesis. Results 15.0%(wt) impregnated MC-PMMA significantly lowered compressive modulus while little affected compressive strength and solidification. MC-PMMA bone cement was biologically safe and indicated excellent bone tissue compatibility. The bone-cement interface crosslinking was significantly higher in MC-PMMA than control after 6 months implantation in the femur of rabbits. The genes of osteogenesis exhibited significantly higher expression level in MC-PMMA. Conclusions MC-PMMA presented perfect mechanical properties, good biosafety and excellent biocompatibility with bone tissues, which has profoundly clinical values.

Preliminary screening of differentially expressed circulating microRNAs in patients with steroid‑induced osteonecrosis of the femoral head

microRNAs have been shown to be stable and detectable in circulating blood, and circulating microRNAs are specifically expressed in numerous diseases. However, to date, the association between microRNAs and osteonecrosis of the femoral head (ONFH) has remained elusive. It was hypothesized that specific microRNAs in the serum of ONFH patients may participate in the pathogenesis of ONFH. In the present study, therefore, the ONFH‑specific serum microRNAs were screened using deep sequencing technology. Peripheral blood serum was collected from three steroid‑induced ONFH patients with systemic lupus erythematosus (SLE), three SLE controls and three healthy controls, respectively. Total RNA was extracted from the serum and a microRNA cDNA library was built. High‑throughput sequencing was then used to sequence the serum microRNAs of the samples and screen differentially expressed serum microRNAs in patients with steroid‑induced ONFH. 27 differentially expressed microRNAs from ONFH serum were selected; of these, 15 microRNAs were over‑expressed and 12 were under‑expressed compared with SLE controls and healthy controls. The present study showed that abnormally expressed microRNAs existed in the serum of ONFH patients and therefore have the potential to be diagnostic markers.

MicroRNA expression in bone marrow mesenchymal stem cells from mice with steroid-induced osteonecrosis of the femoral head

The present study aimed to identify microRNAs (miRNAs) from bone marrow mesenchymal stem cells (BMSCs) in a rat model of steroid-induced osteonecrosis of the femoral head (ONFH) using Affymetrix GeneChip®. Following identification of miRNAs, the present study aimed to elucidate the molecular mechanisms underlying steroid‑induced ONFH. A total of six C57BL/6J mice were randomly divided into two groups, control and experimental groups (n=3 per group). The mice in the experimental group were subcutaneously injected with 21 mg/kg methylprednisolone for 4 weeks, while the mice in the control group were injected with the identical dose of normal saline. The femoral head was subsequently removed and sectioned. Following sectioning, hematoxylin and eosin staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling were performed to confirm the establishment of the model. To replicate the animal model ex vivo, the bone marrow was isolated. Next, different miRNAs were screened for using GeneChip®, and the key miRNAs were assessed by bioinformatics analysis and their functions were confirmed. Compared with the control, 23 miRNAs in the experimental group were identified, with seven upregulated and 16 downregulated. Of these miRNAs, putative target miRNAs were predicted by bioinformatics analysis, with two being upregulated (miR‑21‑3p and miR‑652‑5p) and five downregulated (miR‑206‑3p, miR‑196a‑5p, miR‑34b‑3p, miR‑34c‑5p and miR‑148a‑3p). The results of reverse transcription‑quantitative polymerase chain reaction were consistent with the gene‑chip results. Steroid‑induced ONFH may cause miRNA changes in BMSCs. Numerous miRNAs regulate osteogenic differentiation and the decrease in miRNA‑196a‑5p may be important in steroid-induced ONFH.

Outcome of total knee arthroplasty combined patelloplasty for end-stage type A hemophilic arthropathy

The aim of this study was to retrospectively evaluate the outcome of total knee arthroplasty for end-stage hemophilic arthropathy, based on effectiveness of operation, the specificity of surgical technique, the complications of TKA operation and the strategy of handling of patella. Nineteen patients (25 knees) with type A hemophilic arthropathy were treated with TKA from June 2003 to February 2010. Average patella thickness was 16.3±0.4mm and all patellas were treated by patelloplasty. The patient followed up data was recorded, which included the information of hospital for special surgery knee score(HSS), range of motion(ROM), post-operative complication, and anterior knee pain. The patients were followed for an average post-operative period of 41months (10 to 78months). The mean preoperative HSS score was 51 (31 to 64). Post-operative HSS score was 91 (75 to 110) when followed-up. ROM was modified to 82 degree (60 to 105), compared with 55 degree (5 to 110) preoperatively. Thirteen patients with flexion contracture were corrected from 19 degree (0 to 45) to 2.7 degree (0 to 10). Four patients complained mild but endurable anterior knee pain. The study concludes that TKA is an effective treatment for end-stage hemophilic arthropathy of knee joint, providing good clinical outcome and improving quality of life. Patella of hemophiliac is relatively thin and osteoporotic. Patelloplasty is useful technique for handling of patella during TKA procedure for hemophiliac, with improved knee function, low and acceptable anterior knee pain rate, low reoperation rate.

Ceramic on Ceramic or Ceramic-on-polyethylene for Total Hip Arthroplasty: A Systemic Review and Meta-analysis of Prospective Randomized Studies

Background: Wear debris of polyethylene has become a restraining factor of the durability for total hip arthroplasty (THA). Ceramic on ceramic (COC) has better wear resistance while the squeaking sound and prosthesis fracture are of concern. It is still a controversy that bearing couples are better for THA. Methods: We performed a systematic review of all English articles identified from PubMed (1966-), Embase (1980-) and the Cochrane Library. Clinical outcomes, complications, revision rates, and radiographic outcomes of COC-THA and ceramic on polyethylene (COP)-THA were compared and evaluated. Results: Eight prospective randomized trials enrolling a total of 1508 patients and 1702 THA surgeries were identified. Our results demonstrated the prosthesis fracture and the squeaking sound is significantly higher in COC group and higher wear rate of the COP. Hip function, loosening rate, dislocation rate, revision rate, and the osteolysis rate were comparable between two groups. According to Grading of Recommendations Assessment, Development and Evaluation system assessment, the strength of evidence was high for prosthesis fracture, dislocation, osteolysis, and moderate for radiolucent line or loosening, hip noise, and revision. Conclusions: Up to now, there is insufficient evidence to identify any clinical advantage of COC compared with COP. Longer follow-up of larger randomized trial is needed to clarify the outcomes.