MicroRNA miR-23a cluster promotes osteocyte differentiation by regulating TGF-β signalling in osteoblasts

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

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Osteocytes are the terminally differentiated cell type of the osteoblastic lineage and have important functions in skeletal homeostasis. Although the transcriptional regulation of osteoblast differentiation has been well characterized, the factors that regulate differentiation of osteocytes from mature osteoblasts are poorly understood. Here we show that miR-23a∼1/427a∼1/424-2 (miR-23a cluster) promotes osteocyte differentiation. Osteoblast-specific miR-23a cluster gain-of-function mice have low bone mass associated with decreased osteoblast but increased osteocyte numbers. By contrast, loss-of-function transgenic mice overexpressing microRNA decoys for either miR-23a or miR-27a, but not miR24-2, show decreased osteocyte numbers. Moreover, RNA-sequencing analysis shows altered transforming growth factor-β (TGF-β) signalling. Prdm16, a negative regulator of the TGF-β pathway, is directly repressed by miR-27a with concomitant alteration of sclerostin expression, and pharmacological inhibition of TGF-β rescues the phenotypes observed in the gain-of-function transgenic mice. Taken together, the miR-23a cluster regulates osteocyte differentiation by modulating the TGF-β signalling pathway through targeting of Prdm16.

Original languageEnglish (US)
Article number15000
JournalNature communications
Volume8
DOIs
StatePublished - Apr 11 2017
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Zeng, H. C., Bae, Y., Dawson, B. C., Chen, Y., Bertin, T., Munivez, E., Campeau, P. M., Tao, J., Chen, R., & Lee, B. H. (2017). MicroRNA miR-23a cluster promotes osteocyte differentiation by regulating TGF-β signalling in osteoblasts. Nature communications, 8, [15000]. https://doi.org/10.1038/ncomms15000