Tiecheng Yu

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

Shockwaves increase T-cell proliferation and IL-2 expression through ATP release, P2X7 receptors, and FAK activation

Shockwaves elicited by transient pressure disturbances are used to treat musculoskeletal disorders. Previous research has shown that shockwave treatment affects T-cell function, enhancing T-cell proliferation and IL-2 expression by activating p38 mitogen-activated protein kinase (MAPK) signaling. Here we investigated the signaling pathway by which shockwaves mediate p38 MAPK phosphorylation. We found that shockwaves at an intensity of 0.18 mJ/mm(2) induce the release of extracellular ATP from human Jurkat T-cells at least in part by affecting cell viability. ATP released into the extracellular space stimulates P2X7-type purinergic receptors that induce the activation of p38 MAPK and of focal adhesion kinase (FAK) by phosphorylation on residues Tyr397 and Tyr576/577. Elimination of released ATP with apyrase or inhibition of P2X7 receptors with the antagonists KN-62 or suramin significantly weakens FAK phosphorylation, p38 MAPK activation, IL-2 expression, and T-cell proliferation. Conversely, addition of exogenous ATP causes phosphorylation of FAK and p38 MAPK. Silencing of FAK expression also reduces these cell responses to shockwave treatment. We conclude that shockwaves enhance p38 MAPK activation, IL-2 expression, and T-cell proliferation via the release of cellular ATP and feedback mechanisms that involve P2X7 receptor activation and FAK phosphorylation.

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.

Death Due to Intra-aortic Migration of Kirschner Wire From the Clavicle: A Case Report and Review of the Literature.

AbstractMigration of orthopedic fixation wires into the ascending aorta though a rare occurrence can have devastating consequences. Therefore, prompt recognition, with immediate and cautious retrieval of the implant is paramount in averting these complications.We present a case of a 5-year-old boy with the intra-aortic migration of a K-wire used for the treatment of a right clavicle fracture. He was transferred to us with a history of syncope, chest pain, and shortness of breath 7 days after K-wire placement, which was performed at another hospital. On CT scan, the wire was found to be partially inside the ascending aorta, which was associated with massive hemopericardium and cardiac tamponade. The patient was taken up for emergency surgery for the removal K-wire and for the management of cardiac temponade. However, the patient developed cardiac arrest during the induction of intravenous anesthesia and endotracheal intubation. The K-wire was retrieved from the thorax via thoracotomy. However, the patient died 10 days after the surgery.As the migration of wires and pins during orthopedic surgery can cause potentially fatal complications, these should be used very cautiously, especially for percutaneous treatment of shoulder girdle fractures. The patients with such implants should be followed frequently, both clinically and radiographically. If migration occurs, the patient should be closely monitored for emergent complications and the K-wire should be extracted immediately.

Shockwaves Inhibit Chondrogenic Differentiation of Human Mesenchymal Stem Cells in Association with Adenosine and A2B Receptors

Extracorporeal shockwave therapy (ESWT) has emerged as the important choice for the treatment of many orthopedic disorders. Our previous mechanistic studies suggest that ESWT promoted osteogenesis of human mesenchymal stem cells (hMSCs) through mechanisms that involve adenosine 5′-triphosphate (ATP) release. In this study, we investigated the effect of ESWT on chondrogenesis of hMSCs. We demonstrate that ESWT treatment caused a significant release of adenosine from hMSCs; ESWT treatment increased the levels of A2B receptor (A2BR) in hMSCs under 3-D culture conditions. ESWT, exogenous adenosine and specialized A2BR agonist suppressed hMSC chondrogenic differentiation through downregulating the expressions of aggrecan (ACAN), Collagen Type I alpha 2(COL1A2), Collagen Type II alpha 1(COL2A1), Sex-Determining Region YBox 9 (SOX9) and Sex-Determining Region YBox 6 (SOX6). Selective A2BR antagonists induced chondrogenic differentiation of hMSCs. This study indicated that shockwave therapy inhibits hMSC chondrogenic differentiation through or partially through regulation of adenosine release and activation of A2B receptor under 3-D culture conditions.

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.

Vacuum sealing drainage therapy in the presence of an external fixation device: A case report

Rationale:Vacuum sealing drainage (VSD) is widely utilized for treating traumatic wounds. Patient concerns:It is particularly difficult and time consuming to use in combination with an external fixator. Diagnoses:This is because the hardware or pins used for fixation interfere with maintaining a seal, resulting in poor adhesion and subsequent air leakage. Interventions:To resolve this problem, we have devised a new method for sealing the wound dressing, while maintaining the required vacuum.When using this technique, a rubber strip is wrapped around each pin in 3 circles outside the plastic drape, and then tightly tied. Outcomes:After completing this procedure, a vacuum is obtained, and any air leakage stops. We employed this technique to treat a cohort of patients in our department over a period of two years, and obtained good healing of soft tissue without air leakage, as well as good clinical outcomes. Lessons:We have observed that patients treated with this method experienced good clinical outcomes without air leakage, and we recommend its use in treating cases where an external fixation device is present.

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.

A novel technique to prevent guide wire related complications while inserting the 4.0 mm cannulated screws

BACKGROUND Cannulated screws (4.0 mm) provide inter-fragmentary compression and stability to fractures. A guide wire is used to define the screw trajectory and hold the fracture fragment while the screw is being inserted. The cannulated shaft typically accommodates a 1.25 mm guide pin. Since the guide pin is very slender and undergoes elastic deformation during insertion, there is a high probability of pin breakage. METHODS The authors have devised a new way to place the 4.0 mm cannulated screws in a manner that prevents the intraoperative complication of guide wire breakage. For this technique, predrilling was achieved using a 2.0 mm K-wire which was subsequently replaced with a 1.25 mm guide pin under the protection of sleeve. 4.0 mm cannulated screws were then inserted into a defined trajectory over the guide pin. RESULTS Using the technique, over 20 patients were managed in our department over a period of two years without any complications. CONCLUSION We have observed that patients treated with this method experience short operation time, combined with good clinical outcome and we recommend its use in cases where cannulated screw use is warranted.