Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2002-2-21
pubmed:abstractText
Bisphosphonates are potent antiresorptive drugs commonly employed in the treatment of metabolic bone diseases. Despite their frequent use, the mechanisms of bisphosphonates on bone cells have largely remained unclear. Receptor activator of nuclear factor-kappaB ligand (RANKL) is essential for osteoclast formation and activation, whereas osteoprotegerin (OPG) neutralizes RANKL. Various osteotropic drugs have been demonstrated to modulate osteoblastic production of RANKL and OPG. In this study, we assessed the effects of the bisphosphonates pamidronate (PAM) and zoledronic acid (ZOL) on OPG mRNA steady-state levels (by semiquantitative RT-PCR) and protein production (by ELISA) in primary human osteoblasts (hOB). PAM increased OPG mRNA levels and protein secretion by hOB by up to 2- to 3-fold in a dose-dependent fashion with a maximum effect at 10(-6) M (P < 0.001) after 72 h. Similarly, ZOL enhanced OPG gene expression and protein secretion by hOB in a dose-dependent fashion with a maximum effect at 10(-8) M after 72 h, consistent with the higher biological potency of ZOL. Time course experiments indicated a stimulatory effect of PAM and ZOL on osteoblastic OPG protein secretion by 6-fold, respectively (P < 0.001). Pretreatment with PAM and ZOL prevented the inhibitory effects of the glucocorticoid dexamethasone on OPG mRNA and protein production. Analysis of cellular markers of osteoblastic differentiation revealed that PAM and ZOL induced type I collagen secretion and alkaline phosphatase activity by 2- and 4-fold, respectively (P < 0.0001 by ANOVA). In conclusion, our data suggest that bisphosphonates modulate OPG production by normal human osteoblasts, which may contribute to the inhibition of osteoclastic bone resorption. Since, OPG production increases with osteoblastic cell maturation, enhancement of OPG by bisphosphonates could be related to their stimulatory effects on osteoblastic differentiation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Biological Markers, http://linkedlifedata.com/resource/pubmed/chemical/Collagen Type I, http://linkedlifedata.com/resource/pubmed/chemical/Dexamethasone, http://linkedlifedata.com/resource/pubmed/chemical/Diphosphonates, http://linkedlifedata.com/resource/pubmed/chemical/Glucocorticoids, http://linkedlifedata.com/resource/pubmed/chemical/Glycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles, http://linkedlifedata.com/resource/pubmed/chemical/Osteoprotegerin, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor, http://linkedlifedata.com/resource/pubmed/chemical/TNFRSF11B protein, human, http://linkedlifedata.com/resource/pubmed/chemical/pamidronate, http://linkedlifedata.com/resource/pubmed/chemical/zoledronic acid
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-291X
pubmed:author
pubmed:copyrightInfo
©2002 Elsevier Science (USA).
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
291
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
680-6
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11855844-Biological Markers, pubmed-meshheading:11855844-Cell Differentiation, pubmed-meshheading:11855844-Cells, Cultured, pubmed-meshheading:11855844-Collagen Type I, pubmed-meshheading:11855844-Dexamethasone, pubmed-meshheading:11855844-Diphosphonates, pubmed-meshheading:11855844-Dose-Response Relationship, Drug, pubmed-meshheading:11855844-Glucocorticoids, pubmed-meshheading:11855844-Glycoproteins, pubmed-meshheading:11855844-Humans, pubmed-meshheading:11855844-Imidazoles, pubmed-meshheading:11855844-Kinetics, pubmed-meshheading:11855844-Osteoblasts, pubmed-meshheading:11855844-Osteoprotegerin, pubmed-meshheading:11855844-Protein Biosynthesis, pubmed-meshheading:11855844-RNA, Messenger, pubmed-meshheading:11855844-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:11855844-Receptors, Tumor Necrosis Factor, pubmed-meshheading:11855844-Transcriptional Activation
pubmed:year
2002
pubmed:articleTitle
Bisphosphonates pamidronate and zoledronic acid stimulate osteoprotegerin production by primary human osteoblasts.
pubmed:affiliation
Department of Obstetrics and Gynecology, Georg-August-University of Goettingen, Goettingen, D-37075, Germany. viereck@med.uni-goettingen.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't