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Updated: Apr 28, 2026

Stimulation of Notch Signaling in Mouse Osteoclast Precursors
Published on: February 28, 2017
Downregulation of Notch modulators, tetraspanin 5 and 10, inhibits osteoclastogenesis in vitro
Jian Zhou1,2, Toshifumi Fujiwara2, Shiqiao Ye2
1Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P. R. China.
Abstract:
Genetic studies in human and mice have pinpointed an essential role of Notch signaling in osteoblast and osteoclast differentiation during skeletal development and bone remodeling. However, the factors and pathways regulating Notch activation in bone cells remain largely unknown. In this in vitro study, we have provided evidence that two of the TspanC8 subfamily members of tetraspanins, Tspan-5 and Tspan-10, are up-regulated during osteoclast differentiation and knockdown of their expression by shRNAs dramatically inhibits osteoclastogenesis. Loss of Tspan-5 and Tspan-10 in osteoclast lineage cells results in attenuation of ADAM10 maturation and Notch activation. Therefore, these two tetraspanins play a critical role in osteoclast formation, at least in part, by modulating Notch signaling pathway.
Insights
Two tetraspanins, Tspan-5 and Tspan-10, are crucial for osteoclast differentiation. Their knockdown impairs Notch signaling, highlighting their role in bone cell formation and skeletal development.
Area of Science:
- Bone Biology
- Cell Signaling
- Molecular Genetics
Background:
- Notch signaling is vital for skeletal development and bone remodeling, regulating osteoblast and osteoclast differentiation.
- The specific factors and pathways controlling Notch activation within bone cells are not well understood.
Purpose of the Study:
- To investigate the role of tetraspanins, specifically TspanC8 members, in regulating osteoclast differentiation and Notch signaling.
- To identify novel regulators of Notch pathway activation in bone cells.
Main Methods:
- In vitro study using cell cultures.
- Osteoclast differentiation assays.
- Knockdown of Tspan-5 and Tspan-10 expression using short hairpin RNAs (shRNAs).
- Analysis of ADAM10 maturation and Notch activation levels.
Main Results:
- Tspan-5 and Tspan-10 expression increases during osteoclast differentiation.
- Knockdown of Tspan-5 and Tspan-10 significantly inhibits osteoclastogenesis.
- Loss of Tspan-5 and Tspan-10 leads to reduced ADAM10 maturation and attenuated Notch activation.
Conclusions:
- Tspan-5 and Tspan-10 are critical regulators of osteoclast formation.
- These tetraspanins modulate Notch signaling, playing a key role in osteoclastogenesis.
- The findings reveal a novel mechanism involving TspanC8 tetraspanins in bone cell regulation.
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