title: MicroRNA-17-92 cluster regulates osteoblast proliferation and differentiation.
abstract: MicroRNAs (miRNAs) have been identified to play important functions during osteoblast proliferation, differentiation, and apoptosis. The miR-17~92 cluster is highly conserved in all vertebrates. Loss-of-function of the miR-17-92 cluster results in smaller embryos and immediate postnatal death of all animals. Germline hemizygous deletions of MIR17HG are accounted for microcephaly, short stature, and digital abnormalities in a few cases of Feingold syndrome. These reports indicate that miR-17~92 may play important function in skeletal development and mature. To determine the functional roles of miR-17~92 in bone metabolism as well as osteoblast proliferation and differentiation. Murine embryonic stem cells D3 and osteoprogenitor cell line MC3T3-E1 were induced to differentiate into osteoblasts; the expression of miR-17-92 was assayed by quantitative real-time RT-PCR. The skeletal phenotypes were assayed in mice heterozygous for miR-17~92 (miR-17~92 (+/Δ) ). To determine the possibly direct function of miR-17~92 in bone cells, osteoblasts from miR-17~92 (+/Δ) mice were investigated by ex vivo cell culture. miR-17, miR-92a, and miR-20a within miR-17-92 cluster were expressed at high level in bone tissue and osteoblasts. The expression of miR-17-92 was down-regulated along with osteoblast differentiation, the lowest level was found in mature osteoblasts. Compared to wildtype controls, miR-17-92 (+/Δ) mice showed significantly lower trabecular and cortical bone mineral density, bone volume and trabecular number at 10 weeks old. mRNA expression of Runx2 and type I collagen was significantly lower in bone from miR-17-92 (+/Δ) mice. Osteoblasts from miR-17-92 (+/Δ) mice showed lower proliferation rate, ALP activity and less calcification. Our research suggests that the miR-17-92 cluster critically regulates bone metabolism, and this regulation is mostly through its function in osteoblasts.
authors.affiliation: Laboratory of Endocrinology and Metabolism, West China Hospital, Sichuan University, No. 37 Guoxue Xiang, Chengdu, 610041, People's Republic of China.
authors.forename: Mingliang
authors.initials: M
authors.lastname: Zhou
authors.forename: Junrong
authors.initials: J
authors.lastname: Ma
authors.forename: Shiju
authors.initials: S
authors.lastname: Chen
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.forename: Xijie
authors.initials: X
authors.lastname: Yu
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation; D015536:Down-Regulation / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology; D005838:Genotype; D006706:Homeostasis / Q000235:genetics / Q000502:physiology; D066298:In Vitro Techniques; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D023421:Models, Animal; D010006:Osteoblasts / Q000166:cytology* / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
chemical_list: C575895:MIRN17-92 microRNA, mouse; D035683:MicroRNAs