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

BMB Reports 2019년 52권 9호 p.572 ~ 576
 ( Li Jie ) - Xuzhou Medical University Clinical School Xuzhou Central Hospital Department of Orthopaedics

 ( Li You ) - Nanjing Medical University First Affiliated Hospital Department of Orthopaedics
 ( Wang Shengjie ) - Henan Province People’s Hospital Department of Orthopedics Surgery
 ( Che Hui ) - Nanjing Medical University First Affiliated Hospital Department of Orthopaedics
 ( Wu Jun ) - Nanjing Medical University Department of Anatomy, Histology and Embryology
 ( Ren Yongxin ) - Nanjing Medical University First Affiliated Hospital Department of Orthopaedics

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.

키워드

Bisphosphonates; miR-101-3p; Osteoclast; Osteoporosis; Rap1b
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