File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: N-methyl pyrrolidone as a potent bone morphogenetic protein enhancer for bone tissue regeneration

TitleN-methyl pyrrolidone as a potent bone morphogenetic protein enhancer for bone tissue regeneration
Authors
Issue Date2009
PublisherMary Ann Liebert, Inc. Publishers. The Journal's web site is located at http://www.liebertpub.com/publication.aspx?pub_id=263
Citation
Tissue Engineering - Part A, 2009, v. 15 n. 10, p. 2955-2963 How to Cite?
AbstractIn medicine, N-methyl pyrrolidone (NMP) has a long track record as a constituent in medical devices approved by the Food and Drug Administration and thus can be considered as a safe and biologically inactive small chemical. In the present study, we report on the newly discovered pharmaceutical property of NMP in enhancing bone regeneration in a rabbit calvarial defect model in vivo. At the cellular level, the pharmaceutical effect of NMP was confirmed, in particular, in combination with bone morphogenetic protein (BMP)-2, because NMP increased early and late markers for maturation of preosteoblasts and human bone marrow-derived stem cells in vitro. When we used the multipotent cell line C2C12 without autologous BMP expression, NMP alone had no effect on alkaline phosphatase activity, a marker for osteogenic transdifferentiation. Nevertheless, in combination with low BMP-2 doses, alkaline phosphatase activity was more than eight times as great. Thus, the pharmaceutical NMP mode of action is that of an enhancer of BMP activity. The dependency of the effects of NMP on BMP was confirmed in preosteoblasts because noggin, an extracellular BMP inhibitor, suppressed NMP-induced increases in early markers for osteoblast maturation in vitro. At the molecular level, NMP was shown to have no effect on the binding of BMP-2 to the ectodomain of the high-affinity BMP receptor IA. However, NMP further increased the phosphorylation of p38 and Smad1,5,8 induced by BMP-2. Thus, the small chemical NMP enhances BMP activity by increasing the kinase activity of the BMP receptor complex for Smad1,5,8 and p38 and could be employed as a potent drug for bone tissue regeneration and engineering. © Copyright 2009, Mary Ann Liebert, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/57983
ISSN
2015 SCImago Journal Rankings: 1.500
ISI Accession Number ID
Funding AgencyGrant Number
AO Foundation
Swiss National Funds310000-116240
Funding Information:

The authors would like to thank Inion OY, Tampere, Finland, for the support of M. E. and B. SM. This research work was partly supported by a grant from the AO Foundation (Davos, Switzerland) through the Biotechnology Advisory Board and the Swiss National Funds (310000-116240). We also would like to acknowledge the technical assistance of Alexandr Tchouboukov, Yvonne Bloemhard, and Flora Nichols.

References

 

DC FieldValueLanguage
dc.contributor.authorMiguel, BSen_HK
dc.contributor.authorGhayor, Cen_HK
dc.contributor.authorEhrbar, Men_HK
dc.contributor.authorJung, REen_HK
dc.contributor.authorZwahlen, RAen_HK
dc.contributor.authorHortschansky, Pen_HK
dc.contributor.authorSchmoekel, HGen_HK
dc.contributor.authorWeber, FEen_HK
dc.date.accessioned2010-05-31T03:21:51Z-
dc.date.available2010-05-31T03:21:51Z-
dc.date.issued2009en_HK
dc.identifier.citationTissue Engineering - Part A, 2009, v. 15 n. 10, p. 2955-2963en_HK
dc.identifier.issn1937-3341en_HK
dc.identifier.urihttp://hdl.handle.net/10722/57983-
dc.description.abstractIn medicine, N-methyl pyrrolidone (NMP) has a long track record as a constituent in medical devices approved by the Food and Drug Administration and thus can be considered as a safe and biologically inactive small chemical. In the present study, we report on the newly discovered pharmaceutical property of NMP in enhancing bone regeneration in a rabbit calvarial defect model in vivo. At the cellular level, the pharmaceutical effect of NMP was confirmed, in particular, in combination with bone morphogenetic protein (BMP)-2, because NMP increased early and late markers for maturation of preosteoblasts and human bone marrow-derived stem cells in vitro. When we used the multipotent cell line C2C12 without autologous BMP expression, NMP alone had no effect on alkaline phosphatase activity, a marker for osteogenic transdifferentiation. Nevertheless, in combination with low BMP-2 doses, alkaline phosphatase activity was more than eight times as great. Thus, the pharmaceutical NMP mode of action is that of an enhancer of BMP activity. The dependency of the effects of NMP on BMP was confirmed in preosteoblasts because noggin, an extracellular BMP inhibitor, suppressed NMP-induced increases in early markers for osteoblast maturation in vitro. At the molecular level, NMP was shown to have no effect on the binding of BMP-2 to the ectodomain of the high-affinity BMP receptor IA. However, NMP further increased the phosphorylation of p38 and Smad1,5,8 induced by BMP-2. Thus, the small chemical NMP enhances BMP activity by increasing the kinase activity of the BMP receptor complex for Smad1,5,8 and p38 and could be employed as a potent drug for bone tissue regeneration and engineering. © Copyright 2009, Mary Ann Liebert, Inc.en_HK
dc.languageengen_HK
dc.publisherMary Ann Liebert, Inc. Publishers. The Journal's web site is located at http://www.liebertpub.com/publication.aspx?pub_id=263en_HK
dc.relation.ispartofTissue Engineering - Part Aen_HK
dc.titleN-methyl pyrrolidone as a potent bone morphogenetic protein enhancer for bone tissue regenerationen_HK
dc.typeArticleen_HK
dc.identifier.emailZwahlen, RA:zwahlen@hku.hken_HK
dc.identifier.authorityZwahlen, RA=rp00055en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1089/ten.tea.2009.0009en_HK
dc.identifier.scopuseid_2-s2.0-73349114356en_HK
dc.identifier.hkuros159542en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-73349114356&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume15en_HK
dc.identifier.issue10en_HK
dc.identifier.spage2955en_HK
dc.identifier.epage2963en_HK
dc.identifier.isiWOS:000270553200018-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridMiguel, BS=26032182800en_HK
dc.identifier.scopusauthoridGhayor, C=6603379007en_HK
dc.identifier.scopusauthoridEhrbar, M=7801536855en_HK
dc.identifier.scopusauthoridJung, RE=7201892502en_HK
dc.identifier.scopusauthoridZwahlen, RA=7004217269en_HK
dc.identifier.scopusauthoridHortschansky, P=8511671200en_HK
dc.identifier.scopusauthoridSchmoekel, HG=35270031800en_HK
dc.identifier.scopusauthoridWeber, FE=7201702808en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats