Generation and characterization of a novel shoulder contracture mouse model

Frozen shoulder is a relatively common disorder that leads to severe pain and stiffness in the shoulder joint. Although this disorder is self‐limiting in nature, the symptoms often persist for years, resulting in severe disability. Recent studies using human specimens and animal models have shown distinct changes in the gene expression patterns in frozen shoulder tissue, indicating that novel therapeutic intervention could be achieved by controlling the genes that are potentially involved in the development of frozen shoulder. To achieve this goal, it is imperative to develop a reliable animal joint contracture model in which gene expression can be manipulated by gene targeting and transgenic technologies. Here, we describe a novel shoulder contracture mouse model. We found that this model mimics the clinical presentation of human frozen shoulder and recapitulates the changes in the gene expression pattern and the histology of frozen shoulder and joint contracture in humans and other larger animal models. The model is highly reproducible, without any major complications. Therefore, the present model may serve as a useful tool for investigating frozen shoulder etiology and for identifying its potential target genes. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1732–1738, 2015.     

Acid and duodenogastroesophageal reflux after esophagectomy with gastric tube reconstruction

OBJECTIVE: Patients who undergo esophagectomy with gastric tube reconstruction incur increased risk for acid reflux and duodenogastroesophageal reflux. Few postesophagectomy studies of gastroesophageal reflux disease have included simultaneous 24-h pH and bilirubin monitoring. The aim of this study is to evaluate acid reflux and duodenogastroesophageal reflux after esophagectomy with gastric tube reconstruction. METHODS: Reflux symptom evaluation, endoscopy, and simultaneous 24-h pH and bilirubin monitoring in the cervical esophagus were performed in 25 patients who underwent Ivor Lewis esophagectomy, intrathoracic esophagogastrostomy, and digital dilation of the pyloric ring as treatment for esophageal cancer. RESULTS: Reflux symptoms were severe, mild, and absent in 2, 7, and 16 patients, respectively. Reflux esophagitis and Barrett's esophagus was observed in 11 and 1 patients, respectively. Elevated acid reflux occurred in 7 patients (28%). Elevated duodenogastroesophageal reflux was recorded in 11 patients (44%). Reflux profile analysis identified three patterns: 4 subjects (16%) with both elevated acid reflux and duodenogastroesophageal reflux; 3 (12%) with only elevated acid reflux; and 7 (28%) with only elevated duodenogastroesophageal reflux. Of 7 patients with only elevated duodenogastroesophageal reflux, 4 developed reflux esophagitis. Although reflux symptoms did not correlate with endoscopic esophagitis, a significant correlation was observed between endoscopic esophagitis and acid reflux and/or duodenogastroesophageal reflux. CONCLUSIONS: Reflux symptoms represented a poor indication of esophagitis in patients with esophagectomy and gastric tube reconstruction. Simultaneous 24-h pH and bilirubin monitoring can help in identifying patients at high risk for reflux esophagitis, as well as indicating the cause of esophagitis.     

Wnt2 accelerates cardiac myocyte differentiation from ES-cell derived mesodermal cells via non-canonical pathway

The efficient induction of cardiomyocyte differentiation from embryonic stem (ES) cells is crucial for cardiac regenerative medicine. Although Wnts play important roles in cardiac development, complex questions remain as to when, how and what types of Wnts are involved in cardiogenesis. We found that Wnt2 was strongly up-regulated during cardiomyocyte differentiation from ES cells. Therefore, we investigated when and how Wnt2 acts in cardiogenesis during ES cell differentiation. Wnt2 was strongly expressed in the early developing murine heart. We applied this embryonic Wnt2 expression pattern to ES cell differentiation, to elucidate Wnt2 function in cardiomyocyte differentiation. Wnt2 knockdown revealed that intrinsic Wnt2 was essential for efficient cardiomyocyte differentiation from ES cells. Moreover, exogenous Wnt2 increased cardiomyocyte differentiation from ES cells. Interestingly, the effects on cardiogenesis of intrinsic Wnt2 knockdown and exogenous Wnt2 addition were temporally restricted. During cardiomyocyte differentiation from ES cells, Wnt2 didn't activate canonical Wnt pathway but utilizes JNK/AP-1 pathway which is required for cardiomyocyte differentiation from ES cells. Therefore we conclude that Wnt2 plays strong positive stage-specific role in cardiogenesis through non-canonical Wnt pathway in murine ES cells.     

Massive bone reconstruction with heat‐treated bone graft loaded autologous bone marrow‐derived stromal cells and β‐tricalcium phosphate composites in canine models

Bone marrow‐derived stromal cells (BMSCs) contain mesenchymal stem cells that are capable of forming various mesenchymal tissues. We hypothesized that BMSCs and β‐tricalcium phosphate (β‐TCP) composites would promote the remodeling of large‐sized autologous devitalized bone grafts; therefore, the aim of this study was to evaluate the effects of the composites on the remodeling of autologous devitalized bone grafts. Autologous BMSCs cultured in culture medium containing dexamethasone (10^?7 M) were loaded into porous β‐TCP granules under low‐pressure. Theses BMSC/TCP composites were put into the bone marrow cavity of autologous heat‐treated bone (femoral diaphysis, 65‐mm long, 100°C, 30 min) and put back to the harvest site. In the contralateral side, β‐TCP without BMSC were used in the same manner as the opposite side as the control. Treatment with the BMSC/TCP composites resulted in a significant increase in thickness, bone mineral density, and matured bone volume of the cortical bone at the center of the graft compared to the control. Histological analysis showed matured regenerated bone in the BMSC loaded group. These results indicate that BMSC/TCP composites facilitated bone regeneration and maturation at the graft site of large‐sized devitalized bone. This method could potentially be applied for clinical use in the reconstruction of large bone defects such as those associated with bone tumors. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1308–1316, 2013