Chengxue Wang

Shockwaves Induce Osteogenic Differentiation of Human Mesenchymal Stem Cells Through ATP Release and Activation of P2X7 Receptors

Shockwave treatment promotes bone healing of nonunion fractures. In this study, we investigated whether this effect could be due to adenosine 5′‐triphosphate (ATP) release‐induced differentiation of human mesenchymal stem cells (hMSCs) into osteoprogenitor cells. Cultured bone marrow‐derived hMSCs were subjected to shockwave treatment and ATP release was assessed. Osteogenic differentiation and mineralization of hMSCs were evaluated by examining alkaline phosphatase activity, osteocalcin production, and calcium nodule formation. Expression of P2X7 receptors and c‐fos and c‐jun mRNA was determined with real‐time reverse transcription polymerase chain reaction and Western blotting. P2X7‐siRNA, apyrase, P2 receptor antagonists, and p38 MAPK inhibitors were used to evaluate the roles of ATP release, P2X7 receptors, and p38 MAPK signaling in shockwave‐induced osteogenic hMSCs differentiation. Shockwave treatment released significant amounts (∼7 μM) of ATP from hMSCs. Shockwaves and exogenous ATP induced c‐fos and c‐jun mRNA transcription, p38 MAPK activation, and hMSC differentiation. Removal of ATP with apyrase, targeting of P2X7 receptors with P2X7‐siRNA or selective antagonists, or blockade of p38 MAPK with SB203580 prevented osteogenic differentiation of hMSCs. Our findings indicate that shockwaves release cellular ATP that activates P2X7 receptors and downstream signaling events that caused osteogenic differentiation of hMSCs. We conclude that shockwave therapy promotes bone healing through P2X7 receptor signaling, which contributes to hMSC differentiation. STEM Cells 2013;31:1170–1180

Incidence and risk factors for venous thromboembolism following surgical treatment of fractures below the hip: a meta-analysis.

Venous thromboembolism (VTE) is a common complication after surgical treatment of fractures, which is associated with significant morbidity and mortality. Identifying the risk factors for VTE is important for preventive strategies to reduce the incidence of VTE. Therefore, we conducted a meta‐analysis to evaluate the incidence of VTE and the risk factors influencing the development of VTE in patients who underwent surgery for fractures below the hip. PubMed, Embase, Web of Science, SinoMed (Chinese BioMedical Literature Service System, China) and CNKI (National Knowledge Infrastructure, China) databases were systematically searched to identify cohort or case–control studies that investigated the incidence and risk factors for VTE following surgical treatment of fractures below the hip. VTE risk ratios (RRs) were pooled by use of a fixed‐effect model or a random‐effect model, depending on the heterogeneity among the included studies. Heterogeneity between the studies was assessed by I2 statistics. Twenty‐three studies with a total of 191 294 patients who met the inclusion criteria were included in this meta‐analysis. Our results demonstrated that age (≥60 years) (RR = 1·85, 95% confidence interval (CI): 1·34, 2·55; P = 0·000), previous VTE(RR = 5·25, 95% CI: 2·77, 9·96; P = 0·000), heart failure (RR = 1·74, 95% CI: 1·34, 2·27; P = 0·000), current smoking status (RR = 1·23, 95% CI: 1·07, 1·41; P = 0·004), hypertension (RR = 1·62, 95% CI: 1·27, 2·06; P = 0·000), hyperlipidaemia (RR = 2·16, 95% CI: 1·79, 2·62; P = 0·000), diabetes mellitus (RR = 1·46, 95% CI: 1·27, 1·68; P = 0·000), obesity (RR = 1·58, 95% CI: 1·35,·1·85; P = 0·000), multiple fractures (RR = 2·14, 95% CI: 1·00, 4·60; P = 0·050), varicose veins (RR = 3·07, 95% CI: 1·12, 8·47; P = 0·030), prolonged operation time (weighted mean differences (WMD) = 1·22, 95% CI: 0·63, 1·81; P = 0·000) and prolonged bed rest time (WMD = 3·12, 95% CI: 2·96, 3·29; P = 0·000) were associated with an increased risk of developing VTE. The other variables, including age (<60 years), previous smoking, immobility, pregnancy, cancer, open fractures and combination with trauma were not identified as significant risk factors for VTE. Almost all the risk factors mentioned above are in line with the known risk factors for VTE following surgery for fractures below the hip. Thus, surgeons should pay close attention to patients with these medical conditions in order to reduce the incidence of VTE following surgical treatment of fractures below the hip.

Posterior dislocation of the hip with bilateral femoral fractures: An unusual combination.

Posterior hip dislocation with concomitant femoral fracture is very rare. Here, we report a rare case of a 43-year-old man who was injured in a car accident. The patient sustained right posterior hip dislocation with concomitant right acetabular transverse and posterior wall fracture, ipsilateral femoral shaft fracture, and contralateral proximal femoral fracture (AO type 31-A3). Closed reduction of the hip was attempted, but failed. The acetabular fracture and posterior hip dislocation were reduced and acetabular fracture was fixed using plates through the Kocher-Langenbeck approach. The ipsilateral femoral fracture was treated with closed reduction and intramedullary nailing. The contralateral femoral fracture was treated with closed reduction and Gamma 3 nailing. Postoperative X-rays revealed reduction of the fractures. The patient achieved bone union and recovered function of the hip 4 months after surgery.

Gene markers of fracture healing in early stage and the regulatory mechanism during the process using microarray analysis

Background The aim of this study was to explore crucial markers and uncover the regulatory mechanisms of fracture healing in the early stage. Methods Gene expression profile of GSE45156 was downloaded, in which 3 fractured samples and 3 unfractured samples were used in our present study. Based on the threshold value, differentially expressed genes (DEGs) were selected between two kinds of samples using limma package in R. Enrichment analysis of these DEGs was performed by DAVID software. Furthermore, protein-protein interaction (PPI) network was established integrating information in STRING database, and visualized by Cytoscape software. Results We identified a set of 960 DEGs including 509 up-regulated and 451 downregulated genes. Biological processes involving RNA splicing and cell cycle were significantly enriched for the up-regulated genes such as Snrpd2, Eftud2, Plk1 and Bub1b, whereas skeletal system development and bone development processes were predominant for down-regulated genes like Ubc. In the constructed PPI network, all the five genes were the predominant nodes, of which Snrpd2 was linked to Eftud2, while Bub1b was to interact with Plk1. Conclusion Five candidate genes crucial for indicating the process of fracture in early stage were identified. Eftud2, Snrpd2, Bub1b and Plk1 might function through the involvement of cell-cycle-related BP, while Ubc might influence the protein degradation during bone development. However, more experimental validations are needed to confirm these results.

Fixation of comminuted midshaft clavicle fractures with bone fragments separated by soft tissue using a novel double ligature technique: A case report

Rationale: Clavicle fractures are common, and mostly occur in the midshaft. Methods for operative treatment of midshaft clavicle fractures are evolving, as they improve clinical outcomes compared with traditional conservative management. However, fixation of comminuted midshaft clavicle fractures with bone fragments separated by soft tissue remains a challenge. Patient concerns: Here, we present a case of comminuted midshaft clavicle fracture with a bone fragment separated from the main fracture by soft tissue. Diagnosis: Left comminuted midshaft clavicle fracture. Interventions: We treated this patient with a novel double ligature technique using absorbable suturing. Outcomes: In the past 7 years, we have treated >50 patients with this technique. We have achieved good clinical outcomes with no complications. Lessons: We recommend widespread use of our novel double ligature technique for treating comminuted midshaft clavicle fractures with bone fragments separated by soft tissue.

Identification of key genes influenced by fixation stability in early fracture hematoma and elucidation of their roles in fracture healing

The present study aimed to identify the key genes influenced by fixation stability in early fracture hematoma and to elucidate their roles in fracture healing. The GSE53256 gene expression profile, including six fracture hematoma tissues, was downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) in the fracture hematoma tissues from old rats with rigid fixation compared with semi-rigid fixation were identified using the limma package. Furthermore, Gene Ontology (GO) enrichment analysis for DEGs was performed using BiNGO, and a protein-protein interaction (PPI) network was constructed based on the Search Tool for the Retrieval of Interacting Genes database. A total of 265 DEGs (158 upregulated and 107 downregulated) in the fracture hematoma tissues were screened out. Additionally, the overrepresented GO terms were mainly associated with the extracellular region, positive regulation of locomotion and response to external stimulus. Transforming growth factor, β 1 (Tgfβ1), chemokine (C-X-C motif) ligand 12 (Cxcl12), matrix metallopeptidase 9 (mmp9) and serpin peptidase inhibitor, clade E, member 1 (serpine1) had higher degrees and were hub nodes in the PPI network. In conclusion, fixation stability may influence the fracture healing process, and important DEGs, including Cxcl12, mmp9, Tgfβ1 and serpine1, may be important in this process.

Reduction of acute posterior shoulder dislocation with the FARES method: A case report and a review of the literature.

Posterior shoulder dislocation is a rare entity in clinical practice. The FARES (Fast, Reliable, Safe) method is a well-validated, effective, and rapid approach to achieve reduction of anterior shoulder dislocation, but its use for posterior shoulder dislocation has not been reported previously. A 46-year-old man was admitted to our hospital with acute posterior shoulder dislocation due to a fall experienced while inebriated. We used the FARES method to achieve successful reduction of this case of acute posterior shoulder dislocation without general anesthesia.

Bioinformatics analysis of gene expression profile in callus tissues of osteoporotic phenotype mice induced by osteoblast-specific Krm2 overexpression

The aim of this study was to explore the molecular mechanism of fracture healing in osteoporotic mice.