Abstract

The emerging endocannabinoid system (ECS; comprising the endogenous lipid mediators endocannabinoids [eCBs], produced in virtually all tissues; their metabotropic and ionotropic cannabinoid receptors; biosynthetic pathways and metabolizing enzymes) has been implicated in multiple regulatory functions of the human body. Namely, the ECS and its “tone”, defined by the local levels of eCBs, were shown to control major functions of the central nervous system as well as of multiple peripheral organs (e.g. liver and other metabolic tissues, skin, cardiovascular and pulmonary systems, etc.). Recent studies have intriguingly suggested the existence of a functional ECS in the immune system. Indeed, most immune cells functionally express the bioactive eCBs and the ECS where their activities chiefly exert immune-suppressive and anti-inflammatory actions.

The ECS is functionally active in the joints as well. Importantly, the “eCB tone” was shown to modulate various symptoms and pathogenetic steps of rheumatoid arthritis (RA) and osteoarthritis (OA) in several models of the diseases. Indeed, activation of type-2 cannabinoid receptors (CB2) suppresses cytokine release, inhibits functions of various cells of innate and adaptive immunity, and conveys anti-inflammatory actions. Moreover, stimulation of CB1/CB2 receptors results in analgesic, anti-proliferative, and osteogenetic effects. Interestingly, with respect to fibroblast functions, CB2-coupled signaling exerts anti-fibrotic action whereas, conversely, engagement of CB1 mostly leads to augmentation of fibroblast proliferation.

This presentation reviews the current state-of-the-art of the role of the ECS in the biology of the joints. Moreover, it delineates novel, promising ECS-targeted therapeutic possibilities where synthetic, semi-synthetic or naturally occurring (e.g. from the Cannabis sativa plant) modulators of the “ECS-tone” could be successfully employed in the future clinical management of RA and OA.