1. Deletion of β-adrenergic receptor 1, 2, or both leads to different bone phenotypes and response to mechanical stimulation
- Author
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Mary L. Bouxsein, Estelle N. Bianchi, Serge Ferrari, René Rizzoli, Nicolas Bonnet, Dominique D. Pierroz, and Paul A. Baldock
- Subjects
Male ,medicine.medical_specialty ,Bone density ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,030209 endocrinology & metabolism ,Stimulation ,Bone and Bones ,Bone resorption ,Bone remodeling ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Osteogenesis ,Internal medicine ,medicine ,Animals ,Orthopedics and Sports Medicine ,Femur ,Insulin-Like Growth Factor I ,Receptor ,030304 developmental biology ,ddc:616 ,0303 health sciences ,Osteoblasts ,biology ,Chemistry ,Growth factor ,Isoproterenol ,Organ Size ,Biomechanical Phenomena ,Phenotype ,Endocrinology ,medicine.anatomical_structure ,Gene Expression Regulation ,RANKL ,ddc:618.97 ,Body Composition ,biology.protein ,Bone Remodeling ,Receptors, Adrenergic, beta-2 ,Stress, Mechanical ,Receptors, Adrenergic, beta-1 ,Cancellous bone ,Gene Deletion - Abstract
As they age mice deficient for the ß2 adrenergic receptor (Adrb2( / ) ) maintain greater trabecular bone microarchitecture as a result of lower bone resorption and increased bone formation. The role of ß1 adrenergic receptor signaling and its interaction with ß2 adrenergic receptor on bone mass regulation however remains poorly understood. We first investigated the skeletal response to mechanical stimulation in mice deficient for ß1 adrenergic receptors and/or ß2 adrenergic receptors. Upon axial compression loading of the tibia bone density cancellous and cortical microarchitecture as well as histomorphometric bone forming indices were increased in both Adrb2( / ) and wild type (WT) mice but not in Adrb1( / ) nor in Adrb1b2( / ) mice. Moreover in the unstimulated femur and vertebra bone mass and microarchitecture were increased in Adrb2( / ) mice whereas in Adrb1( / ) and Adrb1b2( / ) double knockout mice femur bone mineral density (BMD) cancellous bone volume/total volume (BV/TV) cortical size and cortical thickness were lower compared to WT. Bone histomorphometry and biochemical markers showed markedly decreased bone formation in Adrb1b2( / ) mice during growth which paralleled a significant decline in circulating insulin like growth factor 1 (IGF 1) and IGF binding protein 3 (IGF BP3). Finally administration of the ß adrenergic agonist isoproterenol increased bone resorption and receptor activator of NF ?B ligand (RANKL) and decreased bone mass and microarchitecture in WT but not in Adrb1b2( / ) mice. Altogether these results demonstrate that ß1 and ß2 adrenergic signaling exert opposite effects on bone with ß1 exerting a predominant anabolic stimulus in response to mechanical stimulation and during growth whereas ß2 adrenergic receptor signaling mainly regulates bone resorption during aging. © 2012 American Society for Bone and Mineral Research.
- Published
- 2012
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