title: MicroRNA functions in osteogenesis and dysfunctions in osteoporosis.
abstract: MicroRNAs (miRNAs) are critical post-transcriptional regulators of gene expression that control osteoblast mediated bone formation and osteoclast-related bone remodeling. Deregulation of miRNA mediated mechanisms is emerging as an important pathological factor in bone degeneration (eg, osteoporosis) and other bone-related diseases. MiRNAs are intriguing regulatory molecules that are networked with cell signaling pathways and intricate transcriptional programs through ingenuous circuits with remarkably simple logic. This overview examines key principles by which miRNAs control differentiation of osteoblasts as they evolve from mesenchymal stromal cells during osteogenesis, or of osteoclasts as they originate from monocytic precursors in the hematopoietic lineage during osteoclastogenesis. Of particular note are miRNAs that are temporally upregulated during osteoblastogenesis (eg, miR-218) or osteoclastogenesis (eg, miR-148a). Each miRNA stimulates differentiation by suppressing inhibitory signaling pathways ('double-negative' regulation). The excitement surrounding miRNAs in bone biology stems from the prominent effects that individual miRNAs can have on biological transitions during differentiation of skeletal cells and correlations of miRNA dysfunction with bone diseases. MiRNAs have significant clinical potential which is reflected by their versatility as disease-specific biomarkers and their promise as therapeutic agents to ameliorate or reverse bone tissue degeneration.
authors.affiliation: Departments of Orthopedic Surgery & Biochemistry and Molecular Biology, Center of Regenerative Medicine, Mayo Clinic, 200 First Street S.W., MSB 3-69, Rochester, MN 55905, USA. vanwijnen.andre@mayo.edu
authors.forename: Andre J
authors.initials: AJ
authors.lastname: van Wijnen
authors.forename: Jeroen
authors.initials: J
authors.lastname: van de Peppel
authors.forename: Johannes P
authors.initials: JP
authors.lastname: van Leeuwen
authors.forename: Jane B
authors.initials: JB
authors.lastname: Lian
authors.forename: Gary S
authors.initials: GS
authors.lastname: Stein
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Westendorf
authors.forename: Merry-Jo
authors.initials: MJ
authors.lastname: Oursler
authors.forename: Hee-Jeong
authors.initials: HJ
authors.lastname: Im
authors.forename: Hanna
authors.initials: H
authors.lastname: Taipaleenmäki
authors.forename: Eric
authors.initials: E
authors.lastname: Hesse
authors.forename: Scott
authors.initials: S
authors.lastname: Riester
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kakar
mesh_terms: D016723:Bone Remodeling; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis / Q000235:genetics*; D010024:Osteoporosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction
chemical_list: D035683:MicroRNAs