Regulation of bone mass, bone loss and osteoclast activity by cannabinoid receptors
Aymen I. Idris,Aymen I. Idris,Rob van't Hof,Rob van't Hof,Iain R. Greig,Susan A Ridge,David Baker,Ruth A. Ross,Stuart H. Ralston,Stuart H. Ralston +9 more
TLDR
The studies show that the CB1 receptor has a role in the regulation of bone mass and ovariectomy-induced bone loss and that CB1- and CB2-selective cannabinoid receptor antagonists are a new class of osteoclast inhibitors that may be of value in the treatment of osteoporosis and other bone diseases.Abstract:
Accelerated osteoclastic bone resorption has a central role in the pathogenesis of osteoporosis and other bone diseases. Identifying the molecular pathways that regulate osteoclast activity provides a key to understanding the causes of these diseases and to the development of new treatments. Here we show that mice with inactivation of cannabinoid type 1 (CB1) receptors have increased bone mass and are protected from ovariectomy-induced bone loss. Pharmacological antagonists of CB1 and CB2 receptors prevented ovariectomy-induced bone loss in vivo and caused osteoclast inhibition in vitro by promoting osteoclast apoptosis and inhibiting production of several osteoclast survival factors. These studies show that the CB1 receptor has a role in the regulation of bone mass and ovariectomy-induced bone loss and that CB1- and CB2-selective cannabinoid receptor antagonists are a new class of osteoclast inhibitors that may be of value in the treatment of osteoporosis and other bone diseases.read more
Citations
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The Endocannabinoid System as an Emerging Target of Pharmacotherapy
TL;DR: A comprehensive overview on the current state of knowledge of the endocannabinoid system as a target of pharmacotherapy is provided.
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Pathogenesis of osteoporosis: concepts, conflicts, and prospects
TL;DR: This review examines the fundamental pathogenetic mechanisms underlying osteoporosis, which include: (a) failure to achieve a skeleton of optimal strength during growth and development; (b) excessive bone resorption resulting in loss of bone mass and disruption of architecture; and (c) Failure to replace lost bone due to defects in bone formation.
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Targeting the endocannabinoid system: to enhance or reduce?
TL;DR: The discovery of compounds that either prolong the lifespan of endocannabinoids or tone down their action for the potential future treatment of pain, affective and neurodegenerative disorders, gastrointestinal inflammation, obesity and metabolic dysfunctions, cardiovascular conditions and liver diseases is discovered.
Journal ArticleDOI
Peripheral cannabinoid receptor, CB2, regulates bone mass
Orr Ofek,Meliha Karsak,Nathalie Leclerc,Meirav Fogel,Baruch Frenkel,Karen L. Wright,Joseph Tam,Malka Attar-Namdar,Vardit Kram,Esther Shohami,Raphael Mechoulam,Andreas Zimmer,Itai Bab +12 more
TL;DR: It is shown that CB2-deficient mice have a markedly accelerated age-related trabecular bone loss and cortical expansion, although cortical thickness remains unaltered, demonstrating that the endocannabinoid system is essential for the maintenance of normal bone mass by osteoblastic and osteoclastic CB2 signaling.
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Endocannabinoid signaling at the periphery: 50 years after THC
Mauro Maccarrone,Itai Bab,Tamás Bíró,Guy A. Cabral,Sudhansu K. Dey,Vincenzo Di Marzo,Justin C. Konje,George Kunos,Raphael Mechoulam,Pal Pacher,Keith A. Sharkey,Andreas Zimmer +11 more
TL;DR: The state of the art of critical eCB functions in peripheral organs is reviewed to establish consensus views on the relevance of the peripheral ECS for human health and disease pathogenesis, as well as highlighting emerging challenges and therapeutic hopes.
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