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Notum disrupts Wnt/β-catenin-mediated BMP9 osteogenesis in MSCs: implications for bone regeneration
Wen-Ge He1,2,3,4, Xin-Yue Wan1,2,3, Yin-Kun Hu4
1Department of Bone and Soft Tissue Tumors, Chongqing University Cancer Hospital, Chongqing, China.
Connective Tissue Research
|November 14, 2025
Summary
NOTUM negatively regulates bone morphogenetic protein 9 (BMP9)-induced osteogenesis by inhibiting the Wnt/β-catenin pathway. This finding highlights NOTUM as a potential therapeutic target for bone regeneration strategies.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Bone morphogenetic protein 9 (BMP9) is a potent osteoinductive cytokine.
- The role of NOTUM, a secreted carboxylesterase, in osteogenic differentiation is not well understood.
Purpose of the Study:
- To investigate the role and mechanism of NOTUM in BMP9-induced osteogenic differentiation of mouse embryonic fibroblasts (MEFs).
Main Methods:
- Overexpression and silencing of Notum in MEFs within a BMP9-induced osteogenic differentiation model.
- Assessment of osteogenic markers (RUNX2, OPN), ALP activity, and matrix mineralization via qPCR, Western blot, and staining.
- In vivo ectopic osteogenesis assays with histochemical staining and micro-CT analysis.
Main Results:
- NOTUM expression is downregulated by BMP9.
- NOTUM attenuated BMP9-induced osteogenic marker expression, ALP activity, and matrix mineralization.
- NOTUM modulated β-catenin and GSK-3β levels, impacting the Wnt/β-catenin signaling pathway.
Conclusions:
- NOTUM acts as a novel regulator of BMP9-induced osteogenesis.
- NOTUM's mechanism involves modulating the Wnt/β-catenin signaling axis.
- NOTUM presents a potential therapeutic target for enhancing bone regeneration.
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