The epigenetically active small chemical N-methyl pyrrolidone (NMP) prevents estrogen depletion induced osteoporosis

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Author(s) Gjoksi, Bebeka, Ghayor, Chafik, Siegenthaler, Barbara M., Ruangsawasdi, Nisarat, Zenobi-Wong, Marcy, Weber, Franz E.
Publication Type Journal Items, Publication Status: Published
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Title The epigenetically active small chemical N-methyl pyrrolidone (NMP) prevents estrogen depletion induced osteoporosis
Author(s) Gjoksi, Bebeka
Ghayor, Chafik
Siegenthaler, Barbara M.
Ruangsawasdi, Nisarat
Zenobi-Wong, Marcy
Weber, Franz E.
Journal or Series Title Bone
Volume Number 78
Start Page 114
End Page 121
ISSN 8756-3282
Publisher Elsevier
Publication Place Amsterdam
Publication Date 2015-09
Keyword(s) Epigenetic
BET proteins
Estrogen deficiency
Abstract Currently, there are several treatments for osteoporosis however; they all display some sort of limitation and/or side effects making the need for new treatments imperative. We have previously demonstrated that NMP is a bioactive drug which enhances bone regeneration in vivo and acts as an enhancer of bone morphogenetic protein (BMP) in vitro. NMP also inhibits osteoclast differentiation and attenuates bone resorption.

In the present study, we tested NMP as a bromodomain inhibitor and for osteoporosis prevention on ovariectomized (OVX) induced rats while treated systemically with NMP. Female Sprague–Dawley rats were ovariectomized and weekly NMP treatment was administrated 1 week after surgery for 15 weeks. Bone parameters and related serum biomarkers were analyzed. 15 weeks of NMP treatment decreased ovariectomy-induced gained weight in average by 43% and improved bone mineral density (BMD) and bone volume over total volume (BV/TV) in rat femur on average by 25% and 41% respectively. Moreover, mineral apposition rate and bone biomarkers of bone turnover in the treatment group were at similar levels with those of the Sham group.

Due to the function of NMP as a low affinity bromodomain inhibitor and its mechanism of action involving osteoblasts/osteoclasts balance and inhibitory effect on inflammatory cytokines, NMP is a promising therapeutic compound for the prevention of osteoporosis.
DOI 10.1016/j.bone.2015.05.004
Additional Notes Received 29 January 2015, Revised 20 April 2015, Accepted 2 May 2015, Published online 7 May 2015
Document Type Article
Publication Status Published
Language English
Assigned Organisational Unit(s) 03949
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NEBIS System Number 004142307
Source Database ID SCOPUS-84929305478
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  author = "Gjoksi, Bebeka and Ghayor, Chafik and Siegenthaler, Barbara M. and Ruangsawasdi, Nisarat and Zenobi-Wong, Marcy and Weber, Franz E.",
  title = "{T}he epigenetically active small chemical {N}-methyl pyrrolidone ({N}{M}{P}) prevents estrogen depletion induced osteoporosis",
  journal = "Bone",
  year = 2015,
  volume = "78",
  pages = "114--121",
  month = sep,

E-Citations record created: Tue, 02 Jun 2015, 08:55:24 CET