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Transcriptional activation of the human osteocalcin gene by basic fibroblast growth factor
Author(s) -
Schedlich Lynette J.,
Flanagan Judith L.,
Crofts Linda A.,
Gillies Susan A.,
Goldberg Daniella,
Morrison Nigel A.,
Eisman John A.
Publication year - 1994
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650090203
Subject(s) - osteocalcin , basic fibroblast growth factor , retinoic acid , osteoblast , fibroblast growth factor , biology , heterologous , microbiology and biotechnology , endocrinology , medicine , growth factor , chemistry , gene , biochemistry , in vitro , alkaline phosphatase , receptor , enzyme
Basic fibroblast growth factor (bFGF) has been detected in bone cells and stimulates osteoblast proliferation; however, its role in the regulation of bone metabolism remains speculative. We demonstrated that the human osteocalcin promoter is activated by bFGF when transfected into rat osteoblastic (ROS 17/2.8) cells. This effect is concentration dependent, with a twofold induction at 10 ng/ml detected after 20 h. The bFGF response is independent of both the 1,25‐dihydroxyvitamin D 3 [1,25‐(OH) 2 D 3 ] and retinoic acid activation of the osteocalcin promoter. To identify the promoter sequences through which bFGF exerts its effect, we tested a series of promoter deletion constructs for their response to bFGF. Deletion of the upstream region between −673 and −588 bp results in a significant loss of induction. Gel‐shift analysis demonstrates that proteins present in ROS 17/2.8 nuclear extracts bind specifically to these sequences. This region alone was unable to confer the bFGF response on a minimal osteocalcin or an heterologous promoter. However, sequences between −678 and −476 bp, which also includes the vitamin D response element (VDRE), were able to confer bFGF inducibility on both a minimal osteocalcin and a heterologous promoter. These data suggest that induction of the human osteocalcin promoter by bFGF requires the interaction of more than one sequence element.