: 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.
Mesenchymal stem cells (MSCs) represent a promising source of cell-based therapies for treatment of a wide variety of injuries and diseases. Their tropism and migration to the damaged sites, which are elicited by cytokines secreted from tissues around pathology, are the prerequisite for tissue repair and regeneration. Better understanding of the elicited-migration of MSCs and discovering conditions that elevate their migration ability, will help to increase their homing to pathologies and improv...
Last. Qing Wang(SDU: Shandong University)H-Index: 3
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Abstract Liver cancer has been considered as one of the major leading causes of cancer-related mortality. The incidence of liver cancer tends to increase in less developed regions. Increasing evidences have demonstrated that mircoRNAs (miRNAs) play crucial roles in the modulation of tumor growth and progression. Whereas, the functional role of miR-539 in hepatocellular carcinoma (HCC) is not well established. In our present study, we sought to explore biological role of miR-539 in HCC progressio...
Last. Yiwen Luo(GU: Guangzhou University)H-Index: 5
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Background Bushen Huoxue decoction (BHD) has a significant effect on fracture rehabilitation, yet its underlying mechanism is still unknown. The purpose of this study was to explore whether BHD promotes bone marrow mesenchymal stem cell (BMSC) migration through the Wnt5a signalling pathway.
#1Xiongbai Zhu(First Affiliated Hospital of Wenzhou Medical University)H-Index: 7
#2Wenjun Lin(First Affiliated Hospital of Wenzhou Medical University)H-Index: 7
Last. Xin Chen(First Affiliated Hospital of Wenzhou Medical University)H-Index: 6
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: This study aims to explore the effects of miR-539 on osteoblast proliferation and differentiation and osteoclast apoptosis in a rat model of osteoporosis, and its mechanism involving the regulation of the AXIN1-mediated wingless-Int (Wnt) signaling pathway. A rat model of osteoporosis was successfully established by ovariectomy. With osteoblasts and osteoclasts of rats not receiving ovariectomy in the sham group as control, those of osteoporotic rats were treated with miR-539 inhibitor, miR-53...
Last. Tingting Tang(SJTU: Shanghai Jiao Tong University)H-Index: 64
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Abstract Fracture nonunion, a serious bone fracture complication, remains a challenge in clinical practice. Although the molecular pathogenesis of nonunion remains unclear, a better understanding may provide better approaches for its prevention, diagnosis and treatment at the molecular level. This review tries to summarise the progress made in studies of the pathogenesis of fracture nonunion. We discuss the evidence supporting the concept that the development of nonunion is related to genetic fa...
Last. Chun-Gen Xing(Soochow University (Suzhou))H-Index: 1
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Background Recent studies have shown that laminin subunit alpha 4 (LAMA4) plays an important role in carcinogenesis. However, its molecular biological function in triple-negative breast cancer (TNBC) has not been entirely clarified. This study investigated the expression of LAMA4 in TNBC and its effect on cell proliferation, migration and invasion. Furthermore, we also identified the potential miRNA directly targeting LAMA4.
Last. Xingguo Chen(Nanjing Medical University)H-Index: 2
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: The present study aimed to investigate the role and mechanism of microRNA-539 (miR-539) in rheumatoid arthritis (RA). A total of 68 RA patients and 46 osteoarthritis patients were enrolled into the current study. Peripheral blood and joint fluid were collected prior to treatment. Reverse transcription-quantitative polymerase chain reaction was performed to detect osteopontin (OPN) mRNA and miR-539 expression levels, while ELISA and western blot analysis were applied to detect OPN protein expre...
Last. Pishan Yang(SDU: Shandong University)H-Index: 17
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Bone defects caused by bone fractures, malformations, post-operation on tumor and even periodontitis have became serious clinical problems. Although the exact origin of osteoblast precursors is still obscure, mesenchymal stem cells (MSCs) that originate from local bone marrow, periosteum, endosteum, mineralized bone or systemic circulation play key roles in osteoblastic differentiation and secretion of multiple factors during spontaneous healing of bone trauma or defect. Substantial evidences ha...
#1Weiping Lin(CUHK: The Chinese University of Hong Kong)H-Index: 8
#2Liangliang Xu(CUHK: The Chinese University of Hong Kong)H-Index: 22
Last. Gang Li(CUHK: The Chinese University of Hong Kong)H-Index: 84
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Summary Cell therapy continues to attract growing interest as a promising approach to treat a variety of diseases. Mesenchymal stem cells (MSCs) have been one of the most intensely studied candidates for cell therapy. Since the homing capacity of MSCs is an important determinant of effective MSC-based therapy, the enhancement of homing efficiency is essential for optimizing the therapeutic outcome. Furthermore, trafficking of endogenous MSCs to damaged tissues, also referred to as endogenic stem...
The chemotactic migration of mesenchymal stem cells (MSCs) is fundamental for their use in cell-based therapies, but little is known about the molecular mechanisms that regulate their directed migration. MicroRNAs (miRNAs) participate in the regulation of a large variety of cellular processes. However, their roles in regulating the responses of MSCs to hepatocyte growth factor (HGF) remain elusive. Here, we found that microRNA-221 (miR-221) and microRNA-26b (miR-26b) were upregulated in MSCs sub...
Mesenchymal stem cells (MSCs) are capable of differentiating into a limited number of diverse cells and secrete regenerative factors that contribute to the repair of damaged tissue. In response to signals emitted by tissue damage, MSCs migrate from the bone marrow and area surrounding blood vessels within tissues into the circulating blood, and accumulate at the site of damage. Hence, MSC transplantation therapy is beginning to be applied to the treatment of various intractable human diseases. R...
: The production of amyloid β (Aβ) and tau hyperphosphorylation have been identified as key processes in Alzheimer's disease (AD) pathogenesis. MiR-539-5p has been found to be abnormally expressed in brain tissue; however, the functional role of miR-539-5p in the pathogenesis of AD remains unclear. In our study, we found that the expression of miR-539-5p was significantly downregulated in humans and mice with AD and was negatively correlated with expression of APP, caveolin 1, and GSK-3β. Moreov...