PMID- 7817811
OWN - NLM
STAT- MEDLINE
DCOM- 19950206
LR  - 20131121
IS  - 0884-0431 (Print)
IS  - 0884-0431 (Linking)
VI  - 9
IP  - 10
DP  - 1994 Oct
TI  - Effects of transforming growth factor beta 1 on the regulation of osteocalcin 
      synthesis in human MG-63 osteosarcoma cells.
PG  - 1635-42
AB  - Treatment of human MG-63 osteosarcoma cells with human recombinant transforming 
      growth factor beta 1 (TGF-beta 1) was found to inhibit cell proliferation. In 
      addition, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]-induced osteocalcin synthesis 
      was greatly influenced by TGF-beta 1. Dose- and time-dependent inhibition was 
      seen both in medium osteocalcin and the corresponding mRNA concentrations. 
      Furthermore, TGF-beta 1 decreased osteocalcin synthesis modulated negatively by 
      dexamethasone or positively by retinoic acid. The stability of osteocalcin mRNA 
      was not decreased by the TGF-beta 1 treatment, but in vitro transcription assays 
      demonstrated diminished osteocalcin gene transcription caused by the TGF-beta 1 
      treatment. Binding of vitamin D receptor (VDR) to an oligonucleotide probe 
      containing the osteocalcin vitamin D response element (VDRE) was not influenced 
      by TGF-beta 1, however. Incubation of the cells with the serine/threonine kinase 
      inhibitor H-7 did not block the ability of TGF-beta 1 to decrease osteocalcin 
      synthesis but caused a further inhibition. Also, the 1,25(OH)2D3-induced 
      osteocalcin synthesis was decreased by H-7 treatment, suggesting that 
      phosphorylation as such is involved in the transcriptional activation mechanism 
      of VDR. These results demonstrate that TGF-beta 1 is a strong inhibitor of the 
      synthesis of osteocalcin, a calcium binding protein participating in bone 
      mineralization, by counteracting the stimulatory effects of other hormones on its 
      synthesis. We further suggest that TGF-beta 1 affects the synthesis of 
      osteocalcin at the level of transcription through mechanism(s) different from the 
      serine/threonine kinase pathway.
FAU - Pirskanen, A
AU  - Pirskanen A
AD  - Department of Biochemistry and Biotechnology, University of Kuopio, Finland.
FAU - Jaaskelainen, T
AU  - Jaaskelainen T
FAU - Maenpaa, P H
AU  - Maenpaa PH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Bone Miner Res
JT  - Journal of bone and mineral research : the official journal of the American 
      Society for Bone and Mineral Research
JID - 8610640
RN  - 0 (Isoquinolines)
RN  - 0 (Oligonucleotide Probes)
RN  - 0 (Piperazines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Vitamin D-Binding Protein)
RN  - 104982-03-8 (Osteocalcin)
RN  - 5688UTC01R (Tretinoin)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - 84477-87-2 (1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - FXC9231JVH (Calcitriol)
SB  - IM
MH  - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
MH  - Base Sequence
MH  - Bone Neoplasms/pathology
MH  - Calcitriol/pharmacology
MH  - Cell Division/drug effects
MH  - Dexamethasone/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Gene Expression Regulation, Neoplastic/drug effects/genetics
MH  - Humans
MH  - Isoquinolines/pharmacology
MH  - Molecular Sequence Data
MH  - Oligonucleotide Probes/chemistry
MH  - Osteocalcin/*antagonists & inhibitors/biosynthesis/genetics
MH  - Osteosarcoma/pathology
MH  - Phosphorylation
MH  - Piperazines/pharmacology
MH  - Protein Kinase C/antagonists & inhibitors
MH  - RNA, Messenger/genetics/metabolism
MH  - Receptors, Calcitriol/metabolism
MH  - Transcription, Genetic/drug effects/genetics
MH  - Transforming Growth Factor beta/*pharmacology
MH  - Tretinoin/pharmacology
MH  - Tumor Cells, Cultured
MH  - Vitamin D-Binding Protein/genetics/metabolism
EDAT- 1994/10/01 00:00
MHDA- 1994/10/01 00:01
CRDT- 1994/10/01 00:00
PHST- 1994/10/01 00:00 [pubmed]
PHST- 1994/10/01 00:01 [medline]
PHST- 1994/10/01 00:00 [entrez]
AID - 10.1002/jbmr.5650091018 [doi]
PST - ppublish
SO  - J Bone Miner Res. 1994 Oct;9(10):1635-42. doi: 10.1002/jbmr.5650091018.