In vivo stimulation of sympathetic nervous system modulates osteoblastic activity in mouse calvaria.
Previously, we demonstrated that epinephrine induced the expression of interleukin (IL)-6 mRNA via beta-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 x kg-1 x 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 beta-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 alpha-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.
Kondo
Ayami
A
Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, Nagoya 464-8650, Japan.
Togari
Akifumi
A
D000818:Animals; D005260:Female; D007276:Injections, Intraventricular; D015850:Interleukin-6 / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D010006:Osteoblasts / Q000502:physiology*; D016627:Oxidopamine; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D012149:Restraint, Physical; D012886:Skull / Q000166:cytology* / Q000294:innervation*; D013563:Sympathectomy, Chemical; D013564:Sympathetic Nervous System / Q000502:physiology*; D013565:Sympatholytics
D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D013565:Sympatholytics; D016627:Oxidopamine