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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1998-4-14
pubmed:abstractText
Estrogen responsiveness of bone is a fundamental regulatory mechanism operative in skeletal homeostasis. We examined the expression of estrogen receptor-alpha (ER) messenger RNA (mRNA) in cultured rat calvarial-derived osteoblasts during progressive development of the osteoblast phenotype. Levels of ER message were compared with the expression of traditional osteoblastic markers that have been mapped throughout the differentiation process of these cells. ER transcripts, measured using semiquantitative RT-PCR analysis, were expressed at low levels in early stage proliferating osteoblasts and increased at confluence upon initial expression of bone cell phenotypic genes. A 23-fold up-regulation of ER mRNA expression coincided with the initiation of alkaline phosphatase activity (day 8). ER mRNA levels progressively increased 70-fold, reaching a maximum level on days 22-25 in fully differentiated osteoblasts when osteocalcin expression peaked, but declined precipitously by day 32 in osteocytic cells. Analysis of RNA isolated directly from rat calvaria confirmed these in vitro results and demonstrated that ER message levels become more abundant postnatally as bone becomes more mineralized. We also examined the responsiveness of osteoblasts to 17beta-estradiol (17beta-E2) at two periods of maturation: the nodule-forming stage (day 14) and the late mineralization stage (day 30). Estradiol suppressed the levels of alkaline phosphatase, osteocalcin, osteonectin, and ER mRNAs on day 14, but up-regulated these messages on day 30. In contrast, 17beta-E2 treatment regulated the steady state levels of transforming growth factor-beta1 and type I procollagen mRNAs only in the late mineralization stage, whereas histone H4 message was unaffected by the steroid at either stage of differentiation. Thus, the observed developmental expression of ER mRNA correlates with progressive osteoblast differentiation and may be a contributing factor to differential regulation of bone cell gene expression by 17beta-E2.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
139
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2048-57
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:9528993-Animals, pubmed-meshheading:9528993-Bone and Bones, pubmed-meshheading:9528993-Calcification, Physiologic, pubmed-meshheading:9528993-Cell Differentiation, pubmed-meshheading:9528993-Cells, Cultured, pubmed-meshheading:9528993-Collagen, pubmed-meshheading:9528993-Estradiol, pubmed-meshheading:9528993-Female, pubmed-meshheading:9528993-Gene Expression Regulation, Developmental, pubmed-meshheading:9528993-Male, pubmed-meshheading:9528993-Osteoblasts, pubmed-meshheading:9528993-Polymerase Chain Reaction, pubmed-meshheading:9528993-RNA, Messenger, pubmed-meshheading:9528993-Rats, pubmed-meshheading:9528993-Receptors, Estrogen, pubmed-meshheading:9528993-Time Factors, pubmed-meshheading:9528993-Transforming Growth Factor beta, pubmed-meshheading:9528993-Up-Regulation
pubmed:year
1998
pubmed:articleTitle
Estrogen receptor-alpha is developmentally regulated during osteoblast differentiation and contributes to selective responsiveness of gene expression.
pubmed:affiliation
Women's Health Research Institute, Wyeth-Ayerst, Radnor, Pennsylvania 19087, USA. bodinep@war.wyeth.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't