This is OSTEOPOROSIS Month
OSTEOPROSIS and BONE FORMATION
Question to be answered: Use VitaminCBD™ to produce elevated Lysyl hydroxylase level in a mouse OSTEOPROSIS model. Is there a dose response?
Bone remodeling in the Endocannabinoid System (ECS) 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 ECS, including endogenous cannabinoid ligands (ECs), cannabinoid receptors (CBRs), and the enzymes responsible for endogenous ligand synthesis and breakdown, is extremely intriguing and complex.
The connection between the ECS and skeletal health; is regulated with the potential use of cannabinoid receptor ligands in the treatment of bone diseases associated with accelerated osteoclastic bone resorption.
Both THC and CBD target CB1 and CB2 receptors are found throughout the brain and central nervous system. THC interacts directly with CB1 and CB2 receptors while CBD does not bind directly to either receptor but acts on them, and other receptors, through indirect means.
Research has shown CBD oil to aid in bone fracture repair. In a study published in the Journal of Bone and Mineral Research conducted by researchers at the Hebrew University of Jerusalem and Tel Aviv University, CBD was found to accelerate the healing of bone fractures by stimulating lysyl hydroxylase activity in osteoblasts, which are bone-building cells. Lysyl hydroxylase is an enzyme that activates collagen crosslinking in bone healing.
CBD has been found to increase lysyl hydroxylase activity, but it was also found to significantly enhance the mechanical properties and strength of the bone. In fact, Dr. Yankel Gabet from Tel Aviv University, one of the lead researchers on the study, said, “After being treated with CBD, the healed bone will be harder to break in the future.”
As mentioned above, CBD can help facilitate bone growth and repair, but it can also prevent bone loss. Fatty acid amides (FAAs) enable bone remodeling and interact with cannabinoid receptors. The enzyme fatty acid amide hydrolase (FAAH) breaks down bone by breaking down FAAs. CBD blocks the activity of FAAH, preventing it from destroying the FAAs that remodel bone.
A functional ECS is present in several mammalian organs and tissues. Recently, endocannabinoids and their receptors have been reported in the skeleton. Osteoblasts, the bone forming cells, and osteoclasts, the bone resorbing cells, produce the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG) and expressed at CB2 cannabinoid receptors.
Although CB2 receptors has been implicated in pathological processes in the central nervous system and peripheral tissues, the skeleton appears as the main system physiologically regulated by CB2. CB2-deficient mice show a markedly accelerated age-related bone loss and the CNR2 gene (encoding CB2) in women is associated with low bone mineral density. The activation of CB2 attenuates ovariectomy-induced bone loss in mice by restraining bone resorption and enhancing bone formation. Hence synthetic CB2 ligands, which are stable and orally available, provide a basis for developing novel anti-osteoporotic therapies, if we can regulate the Lysyl hydroxylase (author’s conjecture).
Activation of CB1 receptors in sympathetic nerve terminals in bone inhibits norepinephrine release, thus balancing the tonic sympathetic restrain of bone formation. Low levels of CB1 were also reported in osteoclasts. CB1-null mice display a skeletal phenotype that is dependent on the mouse strain, gender, and specific mutation of the CB1 encoding gene, CNR.
These above studies demonstrate that the Endocannabinoid System is essential for the maintenance of normal bone mass by osteoblastic and osteoclastic CB2 signaling. Hence, CB2 offers a molecular target for the diagnosis and treatment of osteoporosis, the most prevalent degenerative disease in developed countries.
Eric I Mitchell MD FACPE
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