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Article

Effect of N-Vinyl-2-Pyrrolidone (NVP), a Bromodomain-Binding Small Chemical, on Osteoblast and Osteoclast Differentiation and Its Potential Application for Bone Regeneration

1
Oral Biotechnology and Bioengineering, Center for Dental Medicine, University of Zurich, 8032 Zurich, Switzerland
2
Center for Applied Biotechnology and Molecular Medicine, University of Zurich, 8057 Zurich, Switzerland
*
Authors to whom correspondence should be addressed.
Current address: Dermatology and Venereology Section, Department of Medicine Solna, Center for Molecular Medicine Karolinska Institutet, 171 76 Solna, Sweden.
Academic Editor: Francesca Paino
Int. J. Mol. Sci. 2021, 22(20), 11052; https://doi.org/10.3390/ijms222011052
Received: 13 August 2021 / Revised: 5 October 2021 / Accepted: 9 October 2021 / Published: 13 October 2021
The human skeleton is a dynamic and remarkably organized organ system that provides mechanical support and performs a variety of additional functions. Bone tissue undergoes constant remodeling; an essential process to adapt architecture/resistance to growth and mechanical needs, but also to repair fractures and micro-damages. Despite bone’s ability to heal spontaneously, certain situations require an additional stimulation of bone regeneration, such as non-union fractures or after tumor resection. Among the growth factors used to increase bone regeneration, bone morphogenetic protein-2 (BMP2) is certainly the best described and studied. If clinically used in high quantities, BMP2 is associated with various adverse events, including fibrosis, overshooting bone formation, induction of inflammation and swelling. In previous studies, we have shown that it was possible to reduce BMP2 doses significantly, by increasing the response and sensitivity to it with small molecules called “BMP2 enhancers”. In the present study, we investigated the effect of N-Vinyl-2-pyrrolidone (NVP) on osteoblast and osteoclast differentiation in vitro and guided bone regeneration in vivo. We showed that NVP increases BMP2-induced osteoblast differentiation and decreases RANKL-induced osteoclast differentiation in a dose-dependent manner. Moreover, in a rabbit calvarial defect model, the histomorphometric analysis revealed that bony bridging and bony regenerated area achieved with NVP-loaded poly (lactic-co-glycolic acid (PLGA) membranes were significantly higher compared to unloaded membranes. Taken together, our results suggest that NVP sensitizes BMP2-dependent pathways, enhances BMP2 effect, and inhibits osteoclast differentiation. Thus, NVP could prove useful as “osteopromotive substance” in situations where a high rate of bone regeneration is required, and in the management of bone diseases associated with excessive bone resorption, like osteoporosis. View Full-Text
Keywords: BMP2; osteoblast; osteoclast; bone regeneration; bromodomain inhibitor; small chemical BMP2; osteoblast; osteoclast; bone regeneration; bromodomain inhibitor; small chemical
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MDPI and ACS Style

Klemmer, V.A.; Khera, N.; Siegenthaler, B.M.; Bhattacharya, I.; Weber, F.E.; Ghayor, C. Effect of N-Vinyl-2-Pyrrolidone (NVP), a Bromodomain-Binding Small Chemical, on Osteoblast and Osteoclast Differentiation and Its Potential Application for Bone Regeneration. Int. J. Mol. Sci. 2021, 22, 11052. https://doi.org/10.3390/ijms222011052

AMA Style

Klemmer VA, Khera N, Siegenthaler BM, Bhattacharya I, Weber FE, Ghayor C. Effect of N-Vinyl-2-Pyrrolidone (NVP), a Bromodomain-Binding Small Chemical, on Osteoblast and Osteoclast Differentiation and Its Potential Application for Bone Regeneration. International Journal of Molecular Sciences. 2021; 22(20):11052. https://doi.org/10.3390/ijms222011052

Chicago/Turabian Style

Klemmer, Viviane A., Nupur Khera, Barbara M. Siegenthaler, Indranil Bhattacharya, Franz E. Weber, and Chafik Ghayor. 2021. "Effect of N-Vinyl-2-Pyrrolidone (NVP), a Bromodomain-Binding Small Chemical, on Osteoblast and Osteoclast Differentiation and Its Potential Application for Bone Regeneration" International Journal of Molecular Sciences 22, no. 20: 11052. https://doi.org/10.3390/ijms222011052

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