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The Bromodomain Inhibitor N-Methyl pyrrolidone Prevents Osteoporosis and BMP-Triggered Sclerostin Expression in Osteocytes.

  • Siegenthaler B Center of Dental Medicine, Oral Biotechnology & Bioengineering, University of Zurich, Plattenstrasse 11, 8032 Zürich, Switzerland. barbara.m.siegenthaler@gmail.com.
  • Ghayor C Center of Dental Medicine, Oral Biotechnology & Bioengineering, University of Zurich, Plattenstrasse 11, 8032 Zürich, Switzerland. chafik.ghayor@usz.ch.
  • Gjoksi-Cosandey B Center of Dental Medicine, Oral Biotechnology & Bioengineering, University of Zurich, Plattenstrasse 11, 8032 Zürich, Switzerland. bebeka.cosandey@gmail.com.
  • Ruangsawasdi N Department of Pharmacology, Faculty of Dentistry, Mahidol University, Bangkok 10400, Thailand. nisarat_mac@hotmail.com.
  • Weber FE Center of Dental Medicine, Oral Biotechnology & Bioengineering, University of Zurich, Plattenstrasse 11, 8032 Zürich, Switzerland. franz.weber@zzm.uzh.ch.
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  • 2018-10-28
Published in:
  • International journal of molecular sciences. - 2018
N-methyl pyrrolidone
bromodomain
osteocyte
osteoporosis
sclerostin
Animals
Bone Morphogenetic Proteins
Cell Survival
Disease Models, Animal
Female
Immunohistochemistry
Mice
Osteocytes
Osteoporosis
Pyrrolidinones
Rats
Rats, Sprague-Dawley
English (1) Background: In an adult skeleton, bone is constantly renewed in a cycle of bone resorption, followed by bone formation. This coupling process, called bone remodeling, adjusts the quality and quantity of bone to the local needs. It is generally accepted that osteoporosis develops when bone resorption surpasses bone formation. Osteoclasts and osteoblasts, bone resorbing and bone forming cells respectively, are the major target in osteoporosis treatment. Inside bone and forming a complex network, the third and most abundant cells, the osteocytes, have long remained a mystery. Osteocytes are responsible for mechano-sensation and -transduction. Increased expression of the osteocyte-derived bone inhibitor sclerostin has been linked to estrogen deficiency-induced osteoporosis and is therefore a promising target for osteoporosis management. (2) Methods: Recently we showed in vitro and in vivo that NMP (N-Methyl-2-pyrrolidone) is a bioactive drug enhancing the BMP-2 (Bone Morphogenetic Protein 2) induced effect on bone formation while blocking bone resorption. Here we tested the effect of NMP on the expression of osteocyte-derived sclerostin. (3) Results: We found that NMP significantly decreased sclerostin mRNA and protein levels. In an animal model of osteoporosis, NMP prevented the estrogen deficiency-induced increased expression of sclerostin. (4) Conclusions: These results support the potential of NMP as a novel therapeutic compound for osteoporosis management, since it preserves bone by a direct interference with osteoblasts and osteoclasts and an indirect one via a decrease in sclerostin expression by osteocytes.
Language
  • English
Open access status
gold
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Persistent URL
https://folia.unifr.ch/global/documents/94407
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