title: MicroRNA-17/20a inhibits glucocorticoid-induced osteoclast differentiation and function through targeting RANKL expression in osteoblast cells.
abstract: Glucocorticoids act on the osteoblasts to up-regulate the expression of RANKL, which is very important in the etiology of glucocorticoid-induced osteoclast differentiation and bone resorption. The mechanisms of this process are still not completely understood. Recent studies have shown that glucocorticoids mediate osteoblast function by decreasing the expression of microRNA-17-92a cluster. Coincidentally, we found that the microRNA-17/20a (microRNA-17, microRNA-20a) seed sequences were also complementary to a sequence conserved in the 3'- untranslated region of RANKL mRNA. Therefore, we hypothesized that glucocorticoids might promote osteoblast-derived RANKL expression by down-regulating microRNA-17/20a, which favors differentiation and function of the osteoclasts. In the present study, Western blot analysis showed that microRNA-17/20a markedly lowered the levels of RANKL protein and attenuated dexamethasone-induced RANKL expression in the osteoblasts. The post-transcriptional repression of RANKL by microRNA-17/20a was further confirmed by the luciferase reporter assay. Furthermore, we found that dexamethasone-induced osteoclast differentiation and function were significantly attenuated in co-culture with osteoblast over-expressed microRNA-17/20a and osteoclast progenitors. These results showed that microRNA-17/20a may play a significant role in glucocorticoid-induced osteoclast differentiation and function by targeting the RANKL expression in osteoblast cells.
authors.affiliation: Department of Orthopedics, Changzheng Hospital, Second Military Medical University of China, Shanghai, China. Electronic address: smmuscg@163.com.
authors.forename: Changgui
authors.initials: C
authors.lastname: Shi
authors.affiliation: Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Orthopaedics and Traumatology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China. Electronic address: jinjin838@hotmail.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Qi
authors.affiliation: Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Orthopaedics and Traumatology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Huang
authors.affiliation: Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Orthopaedics and Traumatology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China.
authors.forename: Min
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Orthopaedics and Traumatology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Orthopaedics and Traumatology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China.
authors.forename: Hanbing
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Orthopaedics and Traumatology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Kang
authors.affiliation: Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Orthopaedics and Traumatology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China.
authors.forename: Niandong
authors.initials: N
authors.lastname: Qian
authors.affiliation: Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Orthopaedics and Traumatology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China.
authors.forename: Qiumeng
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Orthopaedics and Traumatology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China. Electronic address: guolei607@126.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Guo
authors.affiliation: Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Orthopaedics and Traumatology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China.
authors.forename: Lianfu
authors.initials: L
authors.lastname: Deng
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002460:Cell Line; D018920:Coculture Techniques; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005938:Glucocorticoids / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D053245:RANK Ligand / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; D035683:MicroRNAs; C543614:Mirn17 microRNA, mouse; C532375:Mirn20 microRNA, mouse; D053245:RANK Ligand; D003907:Dexamethasone
keywords: Glucocorticoids; Osteoclasts; Osteoporosis; RANKL; microRNA-17/20a