title: miR-21 deficiency inhibits osteoclast function and prevents bone loss in mice.
abstract: MicroRNAs emerge as critical post-transcriptional regulators in bone metabolism. We have previously reported in vitro that miR-21 promotes osteogenesis, while studies have also revealed miR-21 as a regulator of osteoclastogenesis and a promoter of osteoclast differentiation in vitro. However, in vivo data are still lacking in identifying skeletal function of miR-21, particularly its effects on osteoporosis. Here, using miR-21 knockout (miR-21-/-) mice, we investigated effects of miR-21 on bone development, bone remodeling and bone loss. Unexpectedly, miR-21-/-mice demonstrated normal skeletal phenotype in development and maintained osteoblastogenesis in vivo. Besides, miR-21-/-mice showed increased receptor activator of nuclear factor κB ligand (RANKL) and decreased osteoprotegerin (OPG) through miR-21 targeting Sprouty 1 (Spry1). Nevertheless, interestingly, miR-21 deficiency promoted trabecular bone mass accrual physiologically. Furthermore, in pathological states, the protection of bone mass was prominent in miR-21-/-mice. These skeletal effects were attributed to inhibition of bone resorption and osteoclast function by miR-21 deficiency through miR-21 targeting programmed cell death 4 (PDCD4), despite the existence of RANKL. As far as we know, this is the first in vivo evidence of a pro-osteoclastic microRNA. Together, these findings clarified function of miR-21 in bone metabolism, particularly uncovering osteo-protective potential of miR-21 inactivation in osteoporosis.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
authors.forename: Cheng-Hu
authors.initials: CH
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Military Stomatology &National Clinical Research Center for Oral Diseases &Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Bing-Dong
authors.initials: BD
authors.lastname: Sui
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
authors.forename: Fang-Ying
authors.initials: FY
authors.lastname: Du
authors.affiliation: State Key Laboratory of Military Stomatology &National Clinical Research Center for Oral Diseases &Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shuai
authors.affiliation: State Key Laboratory of Military Stomatology &National Clinical Research Center for Oral Diseases &Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Chen-Xi
authors.initials: CX
authors.lastname: Zheng
authors.affiliation: Xi'an Institute of Tissue Engineering and Regenerative Medicine, Xi'an, Shaanxi 710032, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
authors.forename: Xiao-Rui
authors.initials: XR
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Military Stomatology &National Clinical Research Center for Oral Diseases &Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.|Xi'an Institute of Tissue Engineering and Regenerative Medicine, Xi'an, Shaanxi 710032, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001862:Bone Resorption; D055786:Gene Knockout Techniques; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010010:Osteoclasts / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; C531950:MIRN21 microRNA, mouse; D035683:MicroRNAs; C498443:Pdcd4 protein, mouse; D016601:RNA-Binding Proteins