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Updated: Jul 17, 2026

Stimulation of Notch Signaling in Mouse Osteoclast Precursors
08:01

Stimulation of Notch Signaling in Mouse Osteoclast Precursors

Published on: February 28, 2017

CCN3/NOV inhibits BMP-2-induced osteoblast differentiation by interacting with BMP and Notch signaling pathways

Tokutaro Minamizato1, Kei Sakamoto, Tingjiao Liu

  • 1Section of Oral Pathology, Graduate School of Tokyo Medical and Dental University, 1-5-45 Yushima, Tokyo 113-8549, Japan.

Biochemical and Biophysical Research Communications
|January 26, 2007
PubMed

Insights

CCN3 (Cellular Communication Network 3) inhibits bone formation by interfering with BMP-2 signaling. It also activates Notch signaling, which is crucial for its inhibitory effects on osteoblast differentiation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • CCN3/NOV is a matricellular protein implicated in various cellular processes.
  • Osteoblast differentiation is a complex process regulated by multiple signaling pathways.

Purpose of the Study:

  • To investigate the role of CCN3 in osteoblast differentiation.
  • To elucidate the molecular mechanisms underlying CCN3's effects on BMP-2 signaling and osteogenesis.

Main Methods:

  • MC3T3-E1 osteoblastic cells were used for in vitro studies.
  • Adenovirus-mediated gene delivery was employed to introduce CCN3 and BMP-2.
  • Quantitative real-time PCR, immunoprecipitation-western analysis, and reporter assays were performed.

Main Results:

  • CCN3 significantly inhibited BMP-2-induced expression of key osteoblast markers (Runx2, osterix, ALP, osteocalcin).
  • CCN3 interacted with BMP-2, attenuated BMP-2/Smad signaling, and activated Notch signaling components (cleaved Notch1, Hes1, Hey1).
  • The inhibitory effects of CCN3 were dependent on Hey1 expression.

Conclusions:

  • CCN3 inhibits BMP-2-induced osteoblast differentiation.
  • CCN3 exerts its inhibitory effects through the interplay of BMP and Notch signaling pathways.

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