PMID- 9737341
OWN - NLM
STAT- MEDLINE
DCOM- 19981125
LR  - 20190905
IS  - 8756-3282 (Print)
IS  - 1873-2763 (Linking)
VI  - 23
IP  - 3
DP  - 1998 Sep
TI  - Catecholamines stimulate the proliferation and alkaline phosphatase activity of 
      MC3T3-E1 osteoblast-like cells.
PG  - 197-203
AB  - A number of factors have been shown to influence osteoblastic proliferation, 
      including fluoride. Recent observations suggest that heterotrimeric G proteins 
      are probably involved in the mitogenic response induced by this agent, further 
      suggesting a role of guanosine 5'-triphosphate (GTP)-binding protein-coupled 
      receptors (GPCR) in the regulation of osteoblastic cell growth. We therefore 
      explored what mitogenic factors known to activate GPCR can influence the 
      replication of mouse osteoblast-like MC3T3-E1 cells. Among several candidates, 
      epinephrine was found to be a potent mitogen for these cells, and its effect on 
      the growth and differentiation of these cells was further investigated. 
      Deoxyribonucleic acid (DNA) synthesis was dose dependently enhanced by this 
      catecholamine in the concentration range of 1 nmol/L-10 micromol/L. Stimulation 
      of DNA synthesis by catecholamines was in the order of epinephrine > 
      norepinephrine >> isoproterenol, indicating that alpha adrenergic receptors 
      mediated this cellular response. Further analysis with specific adrenergic 
      receptor agonists and antagonists suggested that the mitogenic response induced 
      by epinephrine in MC3T3-E1 cells is mediated by alpha1 adrenergic receptors. In 
      addition to its effect on cell replication, epinephrine also enhanced alkaline 
      phosphatase (ALP) activity in these cells but had little effect on collagen 
      synthesis and osteocalcin production. As for the mitogenic response, the change 
      in ALP activity was found to be mediated by alpha1 adrenergic receptors. Both 
      effects of epinephrine on cell replication and ALP activity were markedly reduced 
      by pretreatment of the cells with pertussis toxin (PTX), suggesting a role of Gi 
      proteins. These effects were also completely blocked by pretreatment of the cells 
      with 50 micromol/L genistein, a nonselective inhibitor of tyrosine kinase. In 
      conclusion, the results indicate that epinephrine enhances replication and ALP 
      activity of MC3T3-E1 osteoblast-like cells via alpha1 adrenergic receptors 
      coupled to Gi proteins. The signaling mechanism probably involves a tyrosine 
      phosphorylation mechanism. These observations suggest that PTX-sensitive G 
      proteins are potent mediators of cell proliferation and ALP activity of 
      osteoblast-like cells in response to factors acting through G protein-coupled 
      receptors.
FAU - Suzuki, A
AU  - Suzuki A
AD  - Department of Medicine, University Hospital of Geneva, Switzerland.
FAU - Palmer, G
AU  - Palmer G
FAU - Bonjour, J P
AU  - Bonjour JP
FAU - Caverzasio, J
AU  - Caverzasio J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Bone
JT  - Bone
JID - 8504048
RN  - 0 (Adrenergic alpha-Agonists)
RN  - 0 (Catecholamines)
RN  - 0 (Virulence Factors, Bordetella)
RN  - EC 2.4.2.31 (Pertussis Toxin)
RN  - EC 3.1.3.1 (Alkaline Phosphatase)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - L628TT009W (Isoproterenol)
RN  - X4W3ENH1CV (Norepinephrine)
RN  - YKH834O4BH (Epinephrine)
SB  - IM
MH  - 3T3 Cells/*drug effects
MH  - Adrenergic alpha-Agonists/*pharmacology
MH  - Alkaline Phosphatase/*metabolism
MH  - Animals
MH  - Catecholamines/*pharmacology
MH  - Cell Differentiation/drug effects
MH  - Cell Division/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Epinephrine/pharmacology
MH  - GTP-Binding Proteins/metabolism
MH  - Isoproterenol/pharmacology
MH  - Mice
MH  - Norepinephrine/pharmacology
MH  - Osteoblasts/*drug effects/enzymology
MH  - Pertussis Toxin
MH  - Virulence Factors, Bordetella
EDAT- 1998/09/16 00:00
MHDA- 1998/09/16 00:01
CRDT- 1998/09/16 00:00
PHST- 1998/09/16 00:00 [pubmed]
PHST- 1998/09/16 00:01 [medline]
PHST- 1998/09/16 00:00 [entrez]
AID - S8756-3282(98)00099-4 [pii]
AID - 10.1016/s8756-3282(98)00099-4 [doi]
PST - ppublish
SO  - Bone. 1998 Sep;23(3):197-203. doi: 10.1016/s8756-3282(98)00099-4.