title: MicroRNA-320a Regulates the Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells by Targeting HOXA10.
abstract: OBJECTIVE
  Human bone marrow-derived mesenchymal stem cells (hMSCs) are a promising cell source for bone engineering owing to their high potential to differentiate into osteoblasts. The bone morphogenetic protein-inducible gene homeobox a10 (HOXA10) is a critical regulator of osteogenesis. The objective of the present study was to identify microR-NAs (miRNAs) targeting HOXA10 and examine the effects on the osteogenic differentiation of hMSCs.
  
  
  METHODS
  Based on in silico analysis, HOXA10-targeting miRNAs were selected and their regulatory roles in osteoblast differentiation were investigated.
  
  
  RESULTS
  Six HOXA10-targeting miRNAs were identifIed by computational analysis, of which miR-320a was selected for further analysis because it was downregulated during osteogenic induction. Overexpression of miR-320a downregulated HOXA10 and significantly inhibited osteogenesis in hMSCs, as determined by the downregulation of the osteogenic markers Runx2, ALP, and OC and the inhibition of ALP activity and matrix mineralization, whereas miR-320a inhibition had the opposite effects. Furthermore, ectopic expression of HOXA10 (not including 3'-UTR) rescued the effects of miR-320a on osteogenic differentiation.
  
  
  CONCLUSIONS
  These results suggest that miR-320a acts as a critical regulator of osteogenic differentiation of hMSCs by repressing its target HOXA10.
authors.affiliation: Department of Orthopedics, The 188th Hospital of PLA, ChaoZhou, GuangDong Province, China.
authors.forename: Jianhou
authors.initials: J
authors.lastname: Huang
authors.forename: Yake
authors.initials: Y
authors.lastname: Meng
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Haisong
authors.initials: H
authors.lastname: Yang
authors.forename: Deyu
authors.initials: D
authors.lastname: Chen
authors.forename: Jiangang
authors.initials: J
authors.lastname: Shi
authors.forename: Yongfei
authors.initials: Y
authors.lastname: Guo
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis; D016415:Sequence Alignment
chemical_list: D020413:3' Untranslated Regions; D050659:Core Binding Factor Alpha 1 Subunit; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D015675:Osteocalcin; C069634:HOXA10 protein, human; D000469:Alkaline Phosphatase