Vol. 275, Issue 4, R1099-R1105, October 1998
Endothelins inhibit the mineralization of osteoblastic
MC3T3-E1 cells through the A-type endothelin receptor
Yoshiharu
Hiruma1,
Atsuto
Inoue1,
Aiko
Shiohama1,
Eri
Otsuka1,
Shigehisa
Hirose2,
Akira
Yamaguchi3, and
Hiromi
Hagiwara1
1 Research Center for
Experimental Biology and
2 Department of Biological
Sciences, Tokyo Institute of Technology, Yokohama 226-8501; and
3 Department of Oral
Pathology, School of Dentistry, Showa University, Tokyo 142-8555, Japan
We examined the effects of various
endothelins on the mineralization of mouse clonal preosteoblastic
MC3T3-E1 cells. MC3T3-E1 cells expressed mRNAs for endothelin (ET)-1
and the A-type receptor for ET
(ETA). A pharmacological study
also demonstrated the predominant expression of the
ETA receptor. Northern blotting
analysis revealed that ETs decreased the expression of mRNA for
osteocalcin, which is a marker protein for the maturation of
osteoblastic cells. ET-1 also decreased in the deposition of calcium by
MC3T3-E1 cells in a dose-dependent manner and it had an inhibitory
effect even at 10
11 M. The
rank order of potency of ETs was ET-1 = ET-2 > ET-3. Brief treatment
with 107 M ET-1 on
days
6-8 alone
suppressed mineralization. ET-1 enhanced the rate of production of
inositol 1,4,5-trisphosphate
(IP3) in MC3T3-E1 cells, but it
had no effect on the rate of production of cAMP. Taken together, our
data indicate that ET-1 might inhibit the mineralization of
osteoblastic cells via an interaction with the
ETA receptor, with generation of
IP3 as the intracellular signal.
osteocalcin; calcium deposition; differentiation; osteoblast
