Biological functions of miR-29b contribute to positive regulation of osteoblast differentiation

Zhaoyong Li, Mohammad Q. Hassan, Mohammed Jafferji, Rami I. Aqeilan, Ramiro Garzon, Carlo M. Croce, Andre J van Wijnen, Janet L. Stein, Gary S. Stein, Jane B. Lian

Research output: Contribution to journalArticle

400 Citations (Scopus)

Abstract

Bone tissue arises from mesenchymal cells induced into the osteoblast lineage by essential transcription factors and signaling cascades. MicroRNAs regulate biological processes by binding to mRNA 3′-untranslated region (UTR) sequences to attenuate protein synthesis. Here we performed microRNA profiling and identified miRs that are up-regulated through stages of osteoblast differentiation. Among these are the miR-29, miR-let-7, and miR-26 families that target many collagens and extracellular matrix proteins. We find that miR-29b supports osteoblast differentiation through several mechanisms. miR-29b decreased and anti-miR-29b increased activity of COL1A1, COL5A3, and COL4A2 3′-UTR sequences in reporter assays, as well as endogenous gene expression. These results support a mechanism for regulating collagen protein accumulation during the mineralization stage when miR-29b reaches peak levels. We propose that this mechanism prevents fibrosis and facilitates mineral deposition. Our studies further demonstrate that miR-29b promotes osteogenesis by directly down-regulating known inhibitors of osteoblast differentiation, HDAC4, TGFβ3, ACVR2A, CTNNBIP1, and DUSP2 proteins through binding to target 3′-UTR sequences in their mRNAs. Thus, miR-29b is a key regulator of development of the osteoblast phenotype by targeting anti-osteogenic factors and modulating bone extracellular matrix proteins.

Original languageEnglish (US)
Pages (from-to)15676-15684
Number of pages9
JournalJournal of Biological Chemistry
Volume284
Issue number23
DOIs
StatePublished - Jun 5 2009
Externally publishedYes

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Osteoblasts
3' Untranslated Regions
Extracellular Matrix Proteins
MicroRNAs
Bone
Collagen
Biological Phenomena
Messenger RNA
Bone Matrix
Proteins
Protein Binding
Osteogenesis
Gene expression
Minerals
Assays
Fibrosis
Transcription Factors
Tissue
Phenotype
Gene Expression

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Li, Z., Hassan, M. Q., Jafferji, M., Aqeilan, R. I., Garzon, R., Croce, C. M., ... Lian, J. B. (2009). Biological functions of miR-29b contribute to positive regulation of osteoblast differentiation. Journal of Biological Chemistry, 284(23), 15676-15684. https://doi.org/10.1074/jbc.M809787200

Biological functions of miR-29b contribute to positive regulation of osteoblast differentiation. / Li, Zhaoyong; Hassan, Mohammad Q.; Jafferji, Mohammed; Aqeilan, Rami I.; Garzon, Ramiro; Croce, Carlo M.; van Wijnen, Andre J; Stein, Janet L.; Stein, Gary S.; Lian, Jane B.

In: Journal of Biological Chemistry, Vol. 284, No. 23, 05.06.2009, p. 15676-15684.

Research output: Contribution to journalArticle

Li, Z, Hassan, MQ, Jafferji, M, Aqeilan, RI, Garzon, R, Croce, CM, van Wijnen, AJ, Stein, JL, Stein, GS & Lian, JB 2009, 'Biological functions of miR-29b contribute to positive regulation of osteoblast differentiation', Journal of Biological Chemistry, vol. 284, no. 23, pp. 15676-15684. https://doi.org/10.1074/jbc.M809787200
Li, Zhaoyong ; Hassan, Mohammad Q. ; Jafferji, Mohammed ; Aqeilan, Rami I. ; Garzon, Ramiro ; Croce, Carlo M. ; van Wijnen, Andre J ; Stein, Janet L. ; Stein, Gary S. ; Lian, Jane B. / Biological functions of miR-29b contribute to positive regulation of osteoblast differentiation. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 23. pp. 15676-15684.
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