Modulation of Notch1 signaling regulates bone fracture healing.

Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society
Sanja NovakIvo Kalajzic

Abstract

Fracture healing involves interactions of different cell types, driven by various growth factors, and signaling cascades. Periosteal mesenchymal progenitor cells give rise to the majority of osteoblasts and chondrocytes in a fracture callus. Notch signaling has emerged as an important regulator of skeletal cell proliferation and differentiation. We investigated the effects of Notch signaling during the fracture healing process. Increased Notch signaling in osteochondroprogenitor cells driven by overexpression of Notch1 intracellular domain (NICD1) (αSMACreERT2 mice crossed with Rosa-NICD1) during fracture resulted in less cartilage, more mineralized callus tissue, and stronger and stiffer bones after 3 weeks. Periosteal cells overexpressing NICD1 showed increased proliferation and migration in vitro. In vivo data confirmed that increased Notch1 signaling caused expansion of alpha-smooth muscle actin (αSMA)-positive cells and their progeny including αSMA-derived osteoblasts in the callus without affecting osteoclast numbers. In contrast, anti-NRR1 antibody treatment to inhibit Notch1 signaling resulted in increased callus cartilage area, reduced callus bone mass, and reduced biomechanical strength. Our study shows a positive eff...Continue Reading

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Citations

Jan 21, 2021·International Journal of Molecular Sciences·Katia VaraniMonica De Mattei
Feb 13, 2021·International Journal of Molecular Sciences·Tobias M BallhauseJohannes Keller
Jul 3, 2021·Biomedicines·Aleksandra KostinaAnna Malashicheva
Oct 13, 2021·The Journal of Bone and Joint Surgery. American Volume·Philipp Leucht, Thomas A Einhorn

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