miRNA-34c regulates Notch signaling during bone development

Yangjin Bae, Tao Yang, Huan Chang Zeng, Philippe M. Campeau, Yuqing Chen, Terry Bertin, Brian C. Dawson, Elda Munivez, Jianning Tao, Brendan H. Lee

Research output: Contribution to journalArticle

148 Scopus citations

Abstract

During bone homeostasis, osteoblast and osteoclast differentiation is coupled and regulated by multiple signaling pathways and their downstream transcription factors. Here, we show that microRNA 34 (miR-34) is significantly induced by BMP2 during osteoblast differentiation. In vivo, osteoblast-specific gain of miR-34c in mice leads to an age-dependent osteoporosis due to the defective mineralization and proliferation of osteoblasts and increased osteoclastogenesis. In osteoblasts, miR-34c targets multiple components of the Notch signaling pathway, including Notch1, Notch2 and Jag1 in a direct manner, and influences osteoclast differentiation in a non-cell-autonomous fashion. Taken together, our results demonstrate that miR-34c is critical during osteoblastogenesis in part by regulating Notch signaling in bone homeostasis. Furthermore, miR-34c-mediated post-transcriptional regulation of Notch signaling in osteoblasts is one possible mechanism to modulate the proliferative effect of Notch in the committed osteoblast progenitors which may be important in the pathogenesis of osteosarcomas. Therefore, understanding the functional interaction of miR-34 and Notch signaling in normal bone development and in bone cancer could potentially lead to therapies modulating miR-34 signaling.

Original languageEnglish (US)
Article numberdds129
Pages (from-to)2991-3000
Number of pages10
JournalHuman Molecular Genetics
Volume21
Issue number13
DOIs
StatePublished - Jul 1 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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    Bae, Y., Yang, T., Zeng, H. C., Campeau, P. M., Chen, Y., Bertin, T., Dawson, B. C., Munivez, E., Tao, J., & Lee, B. H. (2012). miRNA-34c regulates Notch signaling during bone development. Human Molecular Genetics, 21(13), 2991-3000. [dds129]. https://doi.org/10.1093/hmg/dds129