title: MiR-133a in human circulating monocytes: a potential biomarker associated with postmenopausal osteoporosis.
abstract: BACKGROUND
  Osteoporosis mainly occurs in postmenopausal women, which is characterized by low bone mineral density (BMD) due to unbalanced bone resorption by osteoclasts and formation by osteoblasts. Circulating monocytes play important roles in osteoclastogenesis by acting as osteoclast precursors and secreting osteoclastogenic factors, such as IL-1, IL-6 and TNF-α. MicroRNAs (miRNAs) have been implicated as important biomarkers in various diseases. The present study aimed to find significant miRNA biomarkers in human circulating monocytes underlying postmenopausal osteoporosis.
  
  
  RESULTS
  We used ABI TaqMan® miRNA array followed by qRT-PCR validation in circulating monocytes to identify miRNA biomarkers in 10 high and 10 low BMD postmenopausal Caucasian women. MiR-133a was upregulated (P=0.007) in the low compared with the high BMD groups in the array analyses, which was also validated by qRT-PCR (P=0.044). We performed bioinformatic target gene analysis and found three potential osteoclast-related target genes, CXCL11, CXCR3 and SLC39A1. In addition, we performed Pearson correlation analyses between the expression levels of miR-133a and the three potential target genes in the 20 postmenopausal women. We did find negative correlations between miR-133a and all the three genes though not significant.
  
  
  CONCLUSIONS
  This is the first in vivo miRNA expression analysis in human circulating monocytes to identify novel miRNA biomarkers underlying postmenopausal osteoporosis. Our results suggest that miR-133a in circulating monocytes is a potential biomarker for postmenopausal osteoporosis.
authors.affiliation: Osteoporosis Research Center, School of Medicine, Creighton University, Omaha, Nebraska, United States of America.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Moore
authors.forename: Xian-Hao
authors.initials: XH
authors.lastname: Peng
authors.forename: Xiang
authors.initials: X
authors.lastname: Fang
authors.forename: Joan M
authors.initials: JM
authors.lastname: Lappe
authors.forename: Robert R
authors.initials: RR
authors.lastname: Recker
authors.forename: Peng
authors.initials: P
authors.lastname: Xiao
mesh_terms: D000368:Aged; D001665:Binding Sites; D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density; D001862:Bone Resorption / Q000097:blood / Q000235:genetics; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D054371:Chemokine CXCL11 / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D010010:Osteoclasts / Q000378:metabolism; D015663:Osteoporosis, Postmenopausal / Q000097:blood* / Q000235:genetics*; D054367:Receptors, CXCR3 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; C515202:CXCL11 protein, human; C515187:CXCR3 protein, human; D027682:Cation Transport Proteins; D054371:Chemokine CXCL11; D007375:Interleukin-1; D015850:Interleukin-6; C548234:MIRN133 microRNA, human; D035683:MicroRNAs; D054367:Receptors, CXCR3; C403517:SLC39A1 protein, human; D014409:Tumor Necrosis Factor-alpha