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MicroRNA-17-92 cluster regulates osteoblast proliferation and differentiation.
MedLine Citation:
PMID:  23673870     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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:
Mingliang Zhou; Junrong Ma; Shiju Chen; Xiang Chen; Xijie Yu
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-5-15
Journal Detail:
Title:  Endocrine     Volume:  -     ISSN:  1559-0100     ISO Abbreviation:  Endocrine     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-5-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9434444     Medline TA:  Endocrine     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Laboratory of Endocrinology and Metabolism, West China Hospital, Sichuan University, No. 37 Guoxue Xiang, Chengdu, 610041, People's Republic of China.
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