β2-Adrenoreceptor ligands regulate osteoclast differentiation in vitro by direct and indirect mechanisms

Sarah J. Aitken, Euphemie Landao-Bassonga, Stuart H. Ralston, Aymen I. Idris

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Pharmacological modulators of β-adrenoceptors can influence bone mineral density and fracture risk in humans. Studies reported that β-adrenoceptor ligands stimulate bone resorption by enhancing the expression of RANK-L, whereas the mechanisms by which β-adrenoreceptors regulate bone formation are poorly understood. Here we show that β2-adrenoceptor is predominantly expressed by bone cells, although low levels of β1- and β3-adrenoceptors were detectable. Noradrenaline and the selective β2-adrenoceptor agonists isoprenaline and salmeterol stimulated osteoclast formation and bone resorption in BM osteoblast co-cultures and increased expression of RANK-L by osteoblasts. All three ligands enhanced RANK-L induced osteoclast formation and increased osteoclast multinuclearity. There was no significant effect of noradrenaline or isoprenaline on osteoblast growth, differentiation or function. These findings confirm the importance of the sympathetic nervous system in the regulation of bone mass, and demonstrate that pharmacological agonists of β2-adrenoceptors directly and indirectly stimulate osteoclast formation, but have no direct effect on osteoblast growth, differentiation or function.

Original languageEnglish
Pages (from-to)96-103
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume482
Issue number1-2
DOIs
Publication statusPublished - 1 Feb 2009
Externally publishedYes

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Osteoclasts
Adrenergic Receptors
Bone
Osteoblasts
Ligands
Bone Resorption
Isoproterenol
Norepinephrine
Pharmacology
RANK Ligand
Bone and Bones
Sympathetic Nervous System
Bone Fractures
Neurology
Growth
Coculture Techniques
Cell culture
Osteogenesis
Bone Density
Modulators

Cite this

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abstract = "Pharmacological modulators of β-adrenoceptors can influence bone mineral density and fracture risk in humans. Studies reported that β-adrenoceptor ligands stimulate bone resorption by enhancing the expression of RANK-L, whereas the mechanisms by which β-adrenoreceptors regulate bone formation are poorly understood. Here we show that β2-adrenoceptor is predominantly expressed by bone cells, although low levels of β1- and β3-adrenoceptors were detectable. Noradrenaline and the selective β2-adrenoceptor agonists isoprenaline and salmeterol stimulated osteoclast formation and bone resorption in BM osteoblast co-cultures and increased expression of RANK-L by osteoblasts. All three ligands enhanced RANK-L induced osteoclast formation and increased osteoclast multinuclearity. There was no significant effect of noradrenaline or isoprenaline on osteoblast growth, differentiation or function. These findings confirm the importance of the sympathetic nervous system in the regulation of bone mass, and demonstrate that pharmacological agonists of β2-adrenoceptors directly and indirectly stimulate osteoclast formation, but have no direct effect on osteoblast growth, differentiation or function.",
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β2-Adrenoreceptor ligands regulate osteoclast differentiation in vitro by direct and indirect mechanisms. / Aitken, Sarah J.; Landao-Bassonga, Euphemie; Ralston, Stuart H.; Idris, Aymen I.

In: Archives of Biochemistry and Biophysics, Vol. 482, No. 1-2, 01.02.2009, p. 96-103.

Research output: Contribution to journalArticle

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