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http://dx.doi.org/10.5483/BMBRep.2019.52.9.076

miR-101-3p/Rap1b signal pathway plays a key role in osteoclast differentiation after treatment with bisphosphonates  

Li, Jie (Department of Orthopaedics, Xuzhou Central Hospital, Clinical School of Xuzhou Medical University)
Li, You (Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University)
Wang, Shengjie (Department of Orthopedics Surgery, Henan Province People's Hospital)
Che, Hui (Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University)
Wu, Jun (The Research Center for Bone and Stem Cells, Department of Anatomy, Histology and Embryology, Nanjing Medical University)
Ren, Yongxin (Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University)
Publication Information
BMB Reports / v.52, no.9, 2019 , pp. 572-576 More about this Journal
Abstract
Bisphosphonates are the mainstay of therapy worldwide for osteoporosis. However, bisphosphonates also have limitations. The objective of this study was to determine the role of miR-101-3p/Rap1b signal pathway in osteoclast differentiation after treatment with bisphosphonates. Our results revealed that miR-101-3p was an important regulator in bisphosphonates treated-osteoclasts. When miR-101-3p was down-regulated in bone marrow-derived macrophage-like cells (BMMs), the development of mature osteoclasts was promoted, and vice versa. However, alendronate decreased multinucleated cell number regardless of whether miR-101-3p was knocked down or over-expressed. TRAP activity assay confirmed the above results. Luciferase assay indicated that miR-101-3p was a negative regulator of Rap1b. Western blot analysis revealed that protein expression level of Rap1b in BMMs transfected with OV-miR-101-3p was lower than that in BMMs transfected with an empty vector. Rap1b overexpression increased TRAP-positive multinucleated cells, while Rap1b inhibition decreased the cell numbers. In vivo data showed that miR-101-3p inhibited osteoclast differentiation in ovariectomized mice while overexpressed of Rap1b blocked the differentiation. Taken together, our data demonstrate that miR-101-3p/Rap1b signal pathway plays a key role in osteoclast differentiation after treatment with bisphosphonates.
Keywords
Bisphosphonates; miR-101-3p; Osteoclast; Osteoporosis; Rap1b;
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