MiR-539-5p negatively regulates migration of rMSCs induced by Bushen Huoxue decoction through targeting Wnt5a.

Bone fractures are very common, and above 5% of the fractures are impaired, leading to nonunions and severe disablilities. The traditional Chinese medicine Bushen Huoxue decoction (BHD) has been used to treat fracture in China. Our previous report has found that BHD promotes migration of rat mesenchymal stem cells (rMSCs) by activating Wnt5a signaling pathway. However, whether and how miRNAs are involved in modulating rMSCs migration induced by BHD has not been explored. In the present study, miRNA microarray analysis and further validation by real-time quantitative RT-PCR revealed that miR-539-5p was down-regulated in BHD-induced rMSCs. Transfection of miR-539-5p mimics suppressed rMSCs migration while the miR-539-5p inhibitor promoted rMSCs migration. Our results suggested that miR-539-5p was a negative regulator of migration of rMSCs induced by BHD. Target prediction analysis tools and Dual-luciferase reporter gene assay identified Wnt5a as a direct target of miR-539-5p. MiR-539-5p inhibited the expression of the Wnt5a and its downstream signaling molecules including JNK, PKC and CaMKII, which played a critical role in regulating migration of rMSCs. Taken together, our results demonstrate that miR-539-5p negatively regulates migration of rMSCs induced by BHD through targeting Wnt5a. These findings provide evidence that miR-539-5p should be considered as an important candidate target for the development of preventive or therapeutic approaches against bone nonunions.

VEGF-loaded mineral-coated microparticles improve bone repair and are associated with increased expression of epo and RUNX-2 in murine non-unions.

A poor vascular supply of the fracture gap is a key factor for the development of atrophic non-unions. Mineral-coated microparticles (MCM) represent a sophisticated carrier system for the delivery of vascular endothelial growth factor (VEGF). Hence, we investigated whether VEGF-loaded MCM improve bone repair in non-unions. For this purpose, we analyzed binding and release kinetics of MCM for VEGF in vitro. Moreover, we applied VEGF-loaded or -unloaded MCM in a murine non-union model in vivo and studied the process of bone healing by means of biomechanical, radiological, histomorphometric, and Western blot techniques. MCM-free non-unions served as controls. The binding efficiency of MCM for VEGF was 46 ± 3% and the release profile revealed an initial minor burst release followed by a sustained release over a 50-day study period, thus, mimicking the physiological expression profile of VEGF during bone healing. In vivo, bone defects treated with VEGF-loaded MCM exhibited a higher bending stiffness, a higher fraction of bone volume/tissue volume and a larger callus area on days 14 and 70 when compared to the other groups. Western blot analyses on day 14 revealed a higher expression of VEGF, erythropoietin (EPO), and runt-related transcription factor 2, but not of EPO-receptor in bone defects treated with VEGF-loaded MCM. These findings demonstrate that the use of MCM for VEGF delivery shows great potential due to the ability to maintain protein stability and functionality in vivo. Moreover, the application of VEGF-loaded MCM represent a promising strategy for the treatment of non-unions. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Teriparatide treatment of femoral fracture nonunion that autogenous bone grafting failed to heal: a case report.

PURPOSE: Management of fracture nonunion is challenging as another surgical intervention for the patient is often a necessity, which has a huge impact on both quality of life and economic burden of the patient. Thus, a less aggressive and better accepted treatment for nonunion is required. METHODS: We gave teriparatide to a 45-year-old man with femoral fracture nonunion 1 year after he underwent surgery with autogenous bone grafting that failed to heal his initial nonunion. Successful union was obtained after once-daily administration of teriparatide for 9 months. RESULTS: Our case showed teriparatide could successfully treat a femoral fracture nonunion that autogenous bone grafting failed to heal. CONCLUSIONS: Teriparatide may provide an alternative treatment for fracture nonunion.

Clinical research on zishengukang pill (see text) used to treat delayed union of fracture.

OBJECTIVE: To observe the curative effect of Zishengukang Pill (see text) on delayed union of fracture. METHODS: Sixty-four patients with delayed union of fracture were randomly divided into a control group of 32 cases treated with Western medicine and a treatment group of 32 cases treated with Western medicine and Zishengukang Pill. After 3 courses of treatment with 30 days as a course, the curative effects in the two groups were evaluated and their clinical symptoms, union rate and union time of fracture were compared. RESULTS: The treatment resulted in cure in 25 cases, improvement in 6 cases and ineffectiveness in 1 case with the effective rate at 96.8% in the treatment group, higher than 81.3% in the control group (P < 0.05). The union rate of fracture in the treatment group was higher than that in the control group (34.3% vs. 12.5%, P < 0.05). The union time of fracture in the treatment group was shorter than that in the control group ((4.0 +/- 1.7) months vs. (5.0 +/- 1.4) months, P < 0.05). CONCLUSION: Zishengukang Pill with obvious curative effect in the treatment of delayed union of fracture is worth popularizing.

Potential role of bone morphogenetic proteins in fracture healing.

Since their discovery, bone morphogenetic proteins have held the promise for use in various orthopaedic diseases. One of the largest areas of likely application is the area of fracture repair. Although millions of fractures occur annually and the majority heal satisfactorily, 5% to 10% go on to delayed union or nonunion. Bone morphogenetic proteins may be able to improve bony healing in these conditions and perhaps enhance the healing of fractures that otherwise heal satisfactorily. This study examines the preclinical data to support the concept of enhancing bony healing and discusses the preliminary data from clinical trials using bone morphogenetic proteins to augment bony healing. Although the potential clinical uses of bone morphogenetic proteins in fracture healing remain significant, this potential has yet to be realized.