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Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, Nagoya 464-8650, Japan
Submitted 21 January 2003 ; accepted in final form 25 April 2003
Previously, we demonstrated that epinephrine induced the expression of
interleukin (IL)-6 mRNA via
-adrenoceptors in cultured human
osteoblastic cells. IL-6 is well known to modulate bone metabolism by
regulating the development and function of osteoclasts and osteoblasts.
Recently, restraint stress and intracerebroventricular injection of
lipopolysaccharide (LPS) have been reported to induce the expression of IL-6
mRNA in peripheral organs in mice in which expression is mediated by the
activation of the sympathetic nervous system. To prove the physiological role
of sympathetic nerves in bone metabolism in vivo, we examined by RT-PCR
analysis the effects of restraint stress and intracerebroventricular injection
of LPS on IL-6 mRNA expression in mouse calvaria. The expression of IL-6 mRNA
in mouse calvaria was stimulated by either restraint stress (30 min) or
intracerebroventricular injection of LPS (50 ng/mouse, 60 min). The treatment
of mice with the neurotoxin 6-hydroxydopamine (6-OHDA, 100 mg ·
kg-1 · day-1 ip for 3 days)
inhibited LPS (icv)-induced expression of IL-6 mRNA in their calvaria. The
expression of IL-6 mRNA induced by the restraint stress was not influenced by
6-OHDA, which destroys noradrenergic nerve terminals. Furthermore,
pretreatment with a
-blocker, propranolol (15 or 25 mg/kg ip), inhibited
both stress- and LPS-induced increases in the level of IL-6 mRNA, but
pretreatment with an
-blocker, phentolamine (5 mg/kg sc), did not
inhibit them in mouse calvaria. In addition, treatment of calvaria with
isoprenaline or norepinephrine increased IL-6 synthesis in the organ culture
system. These results indicate that in vivo adrenergic stimulation modulates
the osteoblastic activity in mouse calvaria via noradrenergic nerve
terminals.
restraint stress; intracerebroventricular injection; interleukin-6; lipopolysaccharide; calvaria; sympathetic activity; osteoblast
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