Abstract
Novel interest has arisen in recent years regarding bone, which is a very complex and dynamic tissue deputed to several functions ranging from mechanical and protective support to hematopoiesis and calcium homeostasis maintenance. In order to address these tasks, a very refined, continuous remodeling process needs to occur involving the coordinated action of different types of bone cells: osteoblasts (OBs), which have the capacity to produce newly formed bone, and osteoclasts (OCs), which can remove old bone. Bone remodeling is a highly regulated process that requires many hormones and messenger molecules, both at the systemic and the local level. The whole picture is still not fully understood, and the role of novel actors, such as the components of the endocannabinoids system (ECS), including endogenous cannabinoid ligands (ECs), cannabinoid receptors (CBRs), and the enzymes responsible for endogenous ligand synthesis and breakdown, is extremely intriguing. This article reviews the connection between the ECS and skeletal health, supporting the potential use of cannabinoid receptor ligands for the treatment of bone diseases associated with accelerated osteoclastic bone resorption, including osteoporosis and bone metastasis.
Highlights
This review summarizes in vitro and in vivo findings on the action of the cannabinoid receptor ligands in skeleton health and pathology, associated with recent advances in the development of highly sensitive analytical methods for the determination and quantization of endogenous cannabinoid ligands (ECs) in plasma and tissue samples
Considering the involvement of the endocannabinoids system (ECS) in bone remodeling, pharmacological modulation of the ECS could offer a possible treatment for pathological conditions where an altered OB/OC activity is observed
CB2R specific ligands are very promising for their beneficial action on bone loss, without causing adverse psychotropic effects
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Many analytical methods for the quantification of the main physiologically occurring cannabinoids, namely AEA and 2-AG, in different biological samples, such as plasma, serum, tissues, saliva, cerebrospinal fluid, and hair from humans, rats, and mice, have been reported in the literature, providing important insights into the physiology and pathology of the ECS and offering new therapeutic perspectives. These analytical methods are essentially based on high-performance liquid chromatography with. The availability of highly sensitive analytical tools allowed a reliable determination of ECs in plasma and tissue samples and can provide a fundamental contribution to the understanding of the physiological and pathophysiological role of the ECS and its potential in the treatment of a large variety of disorders, including neurodegenerative, cardiovascular, metabolic, and bone diseases
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