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

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406 Scopus citations

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

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Li, Z., Hassan, M. Q., Jafferji, M., Aqeilan, R. I., Garzon, R., Croce, C. M., van Wijnen, A. J., Stein, J. L., Stein, G. S., & 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