Many important diseases in otolaryngology manifest through abnormal bone remodeling or destruction. The mechanisms for such pathological remodeling remain poorly understood. Bone is known to be innervated by norepinephrine-containing sympathetic nerves, and sympathectomy is known to induce bone resorption. The role, however, of norepinephrine as a potential bone-modulatory substance is unknown. Using the calvarial calcium release assay, we conducted the following experiment to evaluate the bone-modulatory activity of norepinephrine, the alpha-agonist octopamine, and the beta-agonist isoproterenol. Each agent was tested at 2 concentrations with and without parathyroid hormone. Norepinephrine was found to have no effect on calcium release. In contrast, octopamine at 10–8 mol/l exerted a significant stimulatory effect on calcium release, and isoproterenol at 10–6 mol/l exerted a significant inhibitory effect on parathyroid hormone-induced calcium release. The investigation suggests that a bimodal, concentration-dependent, receptor-specific model for catecholamine-mediated modulation of bone resorption may operate in calvarial bone.
CholeRA. Osteoclasts in chronic otitis media, cholesteatoma, and otosclerosis. Ann Otol Rhinol Laryngol1988; 97: 661–6.
2.
KleinDCRaiszLG. Prostaglandins: Stimulation of bone resorption in tissue culture. Endocrinology1970; 86: 1436–40.
3.
RenWDziakR. Effects of leukotrienes on osteoblastic cell proliferation. Calcif Tissue Int1991; 49: 197–201.
4.
GowenMMundyGR. Control of bone resorption by recombinant immune cell products: Interleukin 1, interleukin 2, and interferon gamma [Abstract]. Bone1986; 7: 157.
5.
KonigAMuhlbauerRCFleischH. Tumor necrosis factor alpha and interleukin-1 stimulate bone resorption in vivo as measured by urinary [3H]tetracycline excretion from prelabeled mice. J Bone Miner Res1988; 3: 621–7.
6.
ShenVKohlerGJeffreyJJPeckWA. Bone-resorbing agents promote and interferon-gamma inhibits bone cell collagenase production. J Bone Miner Res1988; 3: 657–66.
7.
TashjianAHJrVoelkelEFLazzaroM. Alpha and beta human transforming growth factors stimulate prostaglandin production and bone resorption in cultured mouse calvaria. Proc Natl Acad Sci USA1985; 82: 4535–8.
8.
BjurholmAKreicbergsATereniusLGoldsteinMSchultzbergM. Neuropeptide Y–, tyrosine hydroxylase– and vasoactive intestinal peptide-immunoreactive nerves in bone and surrounding tissues. J Auton Nerv Syst1988; 25: 119–25.
9.
CholeRAMcGinnMDTinlingSP. Pressure-induced bone resorption in the middle ear. Ann Otol Rhinol Laryngol1985; 94: 165–70.
10.
FellWA. The effect of sympathectomy on the size of haversian canals in the cat. J Anat1949; 83: 67–8.
11.
SandhuHSHerskovitsMSSinghIJ. Effect of surgical sympathectomy on bone remodeling at rat incisor and molar root sockets. Anat Rec1987; 219: 32–8.
12.
SandhuHSKwong-HingAHerskovitsMSSinghIJ. The early effects of surgical sympathectomy on bone resorption in the rat incisor socket. Arch Oral Biol1990; 35: 1003–7.
13.
HillELTurnerREldeR. Effects of neonatal sympathectomy and capsaicin treatment on bone remodeling in rats. Neuroscience1991; 44: 747–55.
14.
ShermanBECholeRA. In vivo effects of surgical sympathectomy on intramembranous bone resorption. Am J Otol1996; 17: 343–6.
15.
ShermanBECholeRA. Effect of pharmacological sympathectomy on osteoclastic activity in the gerbilline auditory bulla in vivo. Ann Otol Rhinol Laryngol1999; 108: 1078–87.
16.
ShermanBECholeRA. A mechanism for sympathectomy-induced bone resorption in the middle ear. Otolaryngol Head Neck Surg1995; 113: 569–81.
17.
DavidovitchZRosolTShanfeldJ. Direct effects of neurotransmitters on bone resorption in vitro [Abstract]. J Dent Res1990; 69: 206.
18.
CholeRATinlingSP. Adaptive bone modeling in the middle ear is substance-P dependent. Am J Otol1998; 19: 521–4.
19.
von EulerUS. A specific sympathomimetic ergone in adrenergic nerve fibres (sympathin) and its relations to adrenaline and nor-adrenaline. Acta Physiol Scand1946; 12: 73–97.
20.
DuncanCPShimSS. The autonomic nerve supply of bone. An experimental study of the intraosseous adrenergic nervi vasorum in the rabbit. J Bone Joint Surg [Br]1977; 59: 323–30.
21.
BjurholmA. Neuroendocrine peptides in bone. Int Orthop1991; 15: 325–9.
22.
BjurholmAKreicbergsASchultzbergM. Fixation and demineralization of bone tissue for immunohistochemical staining of neuropeptides. Calcif Tissue Int1989; 45: 227–31.
23.
HillELEldeR. Distribution of CGRP-, VIP-, DβH-, SP- and NPY-immunoreactive nerves in the periosteum of the rat. Cell Tissue Res1991; 264: 469–80.
24.
LundbergJMSariaAFranco-CerecedaATheodorsson-NorheimE. Mechanisms underlying changes in the contents of neuropeptide Y in cardiovascular nerves and adrenal gland induced by sympatholytic drugs. Acta Physiol Scand1985; 124: 603–11.
25.
LundbergJMTereniusLHokfeltT. Neuropeptide Y (NPY)-like immunoreactivity in peripheral noradrenergic neurons and effects of NPY on sympathetic function. Acta Physiol Scand1982; 116: 477–80.
26.
BjurholmAKreicbergsASchultzbergMLernerUH. Neuroendocrine regulation of cyclic AMP formation in osteoblastic cell lines (UMR-106-01, ROS 17/2.8, MC3T3-El, and Saos-2) and primary bone cells. J Bone Miner Res1992; 7: 1011–9.
27.
BjurholmAKreicbergsASchultzbergMLernerUH. Parathyroid hormone and noradrenaline-induced enhancement of cyclic AMP in a cloned osteogenic sarcoma cell line (UMR 106) is inhibited by neuropeptideY Acta Physiol Scand1988; 134: 451–2.
28.
GoldhaberP. Tissue culture studies of bone as a model system for periodontal research. J Dent Res1971; 50: 278–87.
29.
GoldhaberPRabadjijaPBeyerWRKornhauserA. Bone resorption in tissue culture and its relevance to periodontal disease. J Am Dent Assoc1973; 87: 1027–33.
30.
RichardsonACTinlingSPCholeRA. Risedronate activity in the fetal and neonatal mouse. Otolaryngol Head Neck Surg1993; 109: 623–33.
31.
DietrichJWGoodsonJMRaiszLG. Stimulation of bone resorption by various prostaglandins in organ culture. Prostaglandins1975; 10: 231–40.
32.
RaiszLGDietrichJWSimmonsHASeyberthHWHubbardWOatesJA. Effect of prostaglandin endoperoxides and metabolites on bone resorption in vitro. Nature1977; 267: 532–4.
33.
ChambersTJMcSheehyPMThomsonBMFullerK. The effect of calcium-regulating hormones and prostaglandins on bone resorption by osteoclasts disaggregated from neonatal rabbit bones. Endocrinology1985; 116: 234–9.
34.
ChambersTJAliNN. Inhibition of osteoclastic motility by prostaglandins I2, E1, E2 and 6-oxo-E1. J Pathol1983; 139: 383–97.
35.
BjurholmAKreicbergsADahlbergLSchultzbergM. The occurrence of neuropeptides at different stages of DBM-induced heterotopic bone formation. Bone Miner1990; 10: 95–107.
36.
GilmoreNVaneJRWyllieJH. Prostaglandins released by the spleen. Nature1968; 218: 1135–40.
37.
MalikKU. Interaction of arachidonic acid metabolites and adrenergic nervous system. Am J Med Sci1988; 295: 280–6.
38.
LevineLMoskowitzMA. α- And β-adrenergic stimulation of arachidonic acid metabolism in cells in culture. Proc Natl Acad Sci USA1979; 76: 6632–6.
39.
VanderwielCJTalmageRV. Comparison of the effects of prostaglandin E2 and parathyroid hormone on plasma calcium concentration and osteoclast function. Endocrinology1979; 105: 588–94.
40.
NorrdinRWShihMS. Systemic effects of prostaglan din E2 on vertebral trabecular remodeling in beagles used in a healing study. Calcif Tissue Int1988; 42: 363–8.
41.
SaffarJLLerouxP. Role of prostaglandins in bone resorption in a synchronized remodeling sequence in the rat. Bone1988; 9: 141–5.
42.
FullerKChambersTJ. Effect of arachidonic acid metabolites on bone resorption by isolated rat osteoclasts. J Bone Miner Res1989; 4: 209–15.
43.
RobinsonDRTashjianAHJrLevineL. Prostaglandin-stimulated bone resorption by rheumatoid synovia. A possible mechanism for bone destruction in rheumatoid arthritis. J Clin Invest1975; 56: 1181–8.
44.
YamasakiKMiuraFSudaT. Prostaglandin as a mediator of bone resorption induced by experimental tooth movement in rats. J Dental Res1980; 59: 1635–42.
45.
ChambersTJFullerKAthanasouNA. The effect of prostaglandins I2, E1, E2 and dibutyryl cyclic AMP on the cytoplasmic spreading of rat osteoclasts. Br J Exp Pathol1984; 65: 557–66.
46.
LernerUHFredholmBBRansjoM. Use of forskolin to study the relationship between cyclic AMP formation and bone resorption in vitro. Biochem J1986; 240: 529–39.
47.
MacDonaldBRGallagherJAAhnfelt-RonneIBeresfordJNGowenMRussellRG. Effects of bovine parathyroid hormone and 1,25-dihydroxyvitamin D3 on the production of prostaglandins by cells derived from human bone. FEBS Lett1984; 169: 49–52.
48.
LernerUH. Parathyroid hormone and transforming growth factor–β synergistically stimulate formation of prostaglandin E2 in neonatal mouse calvarial bones. Acta Physiol Scand1991; 143: 133–4.
