First published online April 24, 2006
Journal of Cell Science 119, 902e (2006)
© The Company of Biologists Limited
MMP13: make NO bones about it
Nitric oxide (NO) is thought to play an important role in bone formation, but its role in the process is poorly understood. Since remodelling of the extracellular matrix by matrix metalloproteinases (MMPs) is crucial for bone development, Carlos Zaragoza and co-workers have examined whether NO and MMPs are connected (see p. 1896). They find that expression of both MMP-13 and the inducible form of NO synthase (iNOS) increases during differentiation of MC3T3-E1 osteoblast cells, as does production of NO. They also show that NO and activated forms of its downstream signalling molecules cGMP and protein kinase G (PKG) can stimulate the activity of the MMP-13 promoter in these cells. Moreover, they can block this effect by mutating a site in the MMP-13 promoter that binds to the transcription factor Cbfa1, a key mediator of bone differentiation. Finally, the authors show that PKG phosphorylates Cbfa1 and that NO-induced expression of MMP-13 is blocked by RNAi directed against Cbfa1. Their results thus indicate that NO regulates bone development by a cGMP-PKG-Cbfa1 pathway that targets MMP-13 and probably other genes.
Related articles in JCS:
- Cbfa-1 mediates nitric oxide regulation of MMP-13 in osteoblasts
- Carlos Zaragoza, Esther López-Rivera, Concepción García-Rama, Marta Saura, Antonio Martínez-Ruíz, Tania R. Lizarbe, Fernando Martín-de-Lara, and Santiago Lamas
JCS 2006 119: 1896-1902.
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