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Abstract Background Interleukin (IL)-17 is an important factor in rheumatoid arthritis (RA) pathogenesis. MicroRNA (miRNA)s are a family of non coding RNAs and associated with human diseases including RA. The purpose of this study is to identify the miRNAs in the differentiation of IL-17 producing cells, and analyze their expression pattern in the peripheral blood mononuclear cells (PBMC) and synovium from RA patients. Methods IL-17 producing cells were expanded from CD4+T cell. MiRNA microarray was performed to identify the miRNAs in the differentiation of IL-17 producing cells. Quantitative polymerase chain reaction was performed to examine the expression patterns of the identified miRNAs in the PBMC and synovium from RA and osteoarthritis (OA) patients. Double staining combining in situ hybridization and immunohistochemistry of IL-17 was performed to analyze the expression pattern of identified miRNA in the synovium. Results Six miRNAs, let-7a, miR-26, miR-146a/b, miR-150, and miR-155 were significantly up regulated in the IL-17 producing T cells. The expression of miR-146a and IL-17 was higher than in PBMC in the patients with low score of Larsen grade and short disease duration. MiR-146a intensely expressed in RA synovium in comparison to OA. MiR-146a expressed intensely in the synovium with hyperplasia and high expression of IL-17 from the patients with high disease activity. Double staining revealed that miR-146a expressed in IL-17 expressing cells. Conclusion These results indicated that miR-146a was associated with IL-17 expression in the PBMC and synovium in RA patients. There is the possibility that miR-146a participates in the IL-17 expression.

This study evaluated factors affecting sensory restoration after thumb reconstruction using a wrap-around flap in 21 thumbs in patients aged 11 to 50 years old. The patients were followed from 12 to 94 months after surgery. Static and moving 2-point discrimination of the reconstructed pulp was measured and analysed using multiple regression analysis. According to the univariate and multivariate analyses, the preoperative period, the number of nerve coaptations, and the duration of follow-up all significantly affected sensory recovery. Sensory recovery with more than three coaptations was significantly better than those with less than three coaptations, and the number of nerve coaptations was one of the primary factors influencing sensory recovery. We conclude from this study that the wrap-around flap should be performed soon after injury and that surgeons should try to coaptate three or more nerves to enhance sensory recovery. Level of evidence: IV [ABSTRACT FROM AUTHOR]

The purpose of this study is to clarify the kinetics of transplanted mesenchymal stem cells (MSCs) in rat skeletal muscle injury model and the contribution of the magnetic cell delivery system to muscle injury repair. A magnetic field generator was used to apply an external magnetic force to the injury site of the tibia anterior muscle, and 1 × 106 MSCs labeled with ferucarbotran-protamine complexes, which were isolated from luciferase transgenic rats, were injected into the injury site. MSCs were injected with and without an external magnetic force (MSC M+ and MSC M− groups, respectively), and phosphate-buffered saline was injected into injury sites as a control. In vivo bioluminescence imaging was performed immediately after the transplantation and, at 12, 24, and 72 h, and 1 and 4 weeks post-transplantation. Also, muscle regeneration and function were histologically and electromechanically evaluated. In vivo bioluminescence imaging showed that the photon of the MSC M+ group was significantly higher than that of the MSC M− group throughout the observation period. In addition, muscle regeneration and function in the MSC M+ group was histologically and functionally better than that of the MSC M− group. The results of our study indicated that magnetic cell delivery system may be of use in directing the transplanted MSCs to the injury site to promote skeletal muscle regeneration. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 754-759, 2013 [ABSTRACT FROM AUTHOR]

Chung Y-G, Bishop AT, Giessler GA, Suzuki O, Platt JL, Pelzer M, Friedrich PF, Kremer T. Surgical angiogenesis: a new approach to maintain osseous viability in xenotransplantation. Xenotransplantation 2010; 17: 38–47. © 2010 John Wiley & Sons A/S. Large segmental osseous defects are challenging clinical problems. Current reconstructive methods, using non-viable allografts, vascularized autografts or prostheses have significant rates of serious complications and failure. These include infection, stress fracture and non-union (frozen structural allogenic bone); loosening and implant failure (prosthetic replacement); limited availability, poor match of size and shape and donor site morbidity (vascularized autograft bone). In the future, microvascular transplantation of living allogenic or xenogenic bone could solve some of these issues, combining the advantages of living bone autografts (capability of primary osseous healing, remodeling, and fracture resistance) with the ability to match size and shape, provide immediate stability and avoid donor site morbidity. Xenotransplants would be particularly attractive, as they could be readily available, if long-term bone survival could be achieved without unacceptable morbidity. Here, we present a preliminary study to evaluate a new and unique method to maintain xenogenic bone circulation without need for long-term immune modulation that depends upon generation of a neo-angiogenic circulation within the transplanted bone from recipient-derived vessels. Thus, only short-term immunosuppression would be required to achieve bone survival. Methods: One hundred and forty-one hamster femora were microsurgically transplanted to rats, restoring nutrient vessel circulation with standard microvascular anastomoses. At the same time, a host-derived arteriovenous bundle (AVB) was placed within the medullary canal. Two independent variables were evaluated: use of tacrolimus/cyclophosmamid immunosuppression (IS) and patency of the implanted AVB. Rats were therefore randomized to four groups; group 1—no IS + patent AVB; group 2—no IS + ligated AVB; group 3—IS + patent AVB; group 4—IS + ligated AVB. Rats were sacrificed after 1 or 2 weeks. We evaluated bone blood flow (microsphere entrapment), neoangiogenesis (microangiography and quantification of capillary density), bone necrosis rate (osteocyte counts) and nutrient pedicle rejection (microsurgical anastomotic patency). Statistical Analysis was performed with two-way ANOVA with Bonferroni adjustment. Differences were considered significant when P < 0.05. Results: Capillary density was significantly increased with a patent intramedullary AVB (groups 1/3) compared to groups with ligated AVBs (groups 3/4). Capillary sprouting was predominantly restricted to the endosteal layer. Most nutrient pedicles (78.7%) stayed patent in groups with IS (groups 3 and 4). Consequently, bone blood flow was significanty higher in groups 3 and 4 compared to groups 1 and 2. Similary, a patent AV bundle improved flow in group 1 when compared to group 2. The bone necrosis rate was not influenced by the presence of patent AVBs but was significantly reduced in groups 3 and 4. Conclusions: Surgical angiogenesis occurs when patent arteriovenous bundles are placed in the medullary canal of xenogenic bone and leads to increased bone blood flow. Bone viability was not significantly influenced by neoangiogenesis. Although capillary sprouting was restricted to the endosteal layer in this short term study, more complete cortical revascularization might be observed in a long-term study. Such a study should further evaluate whether these new vessels supply sufficient blood flow to maintain long-term bone viability and allow remodeling. [ABSTRACT FROM AUTHOR]

This study evaluated factors affecting sensory restoration after thumb reconstruction using a wrap-around flap in 21 thumbs in patients aged 11 to 50 years old. The patients were followed from 12 to 94 months after surgery. Static and moving 2-point discrimination of the reconstructed pulp was measured and analysed using multiple regression analysis. According to the univariate and multivariate analyses, the preoperative period, the number of nerve coaptations, and the duration of follow-up all significantly affected sensory recovery. Sensory recovery with more than three coaptations was significantly better than those with less than three coaptations, and the number of nerve coaptations was one of the primary factors influencing sensory recovery. We conclude from this study that the wrap-around flap should be performed soon after injury and that surgeons should try to coaptate three or more nerves to enhance sensory recovery. Level of evidence: IV.