In this paper, researchers looked at the function of the cannabinoid receptor type 2 (CB2) in the bone loss associated with celiac disease (CD), as well as the effect of pharmacological regulation on osteoclast activity. They previously found a link between the CB2 Q63R variation and CD, indicating that it may be used as a disease biomarker. Furthermore, CB2 stimulation is effective for decreasing osteoclast activity in a variety of bone pathologic situations. In vitro osteoclasts (OCs) were isolated from peripheral blood mononuclear cells of healthy donors, CD children at diagnosis, and after 1 year of gluten-free diet (GFD) and characterized for the expression of CB2 and specific osteoclastic markers, TRAP and Cathepsin K, using real-time PCR and western blot. To assess osteoclast activity before and after 48 hours of exposure to CB2 selective medications and Vitamin D, the TRAP assay and Bone Resorption assay were used. They discovered osteoclast hyperactivation and low CB2 levels in CD patients. CB2 stimulation with JWH-133 agonist reduces osteoclast activity more effectively than Vitamin D, but CB2 inhibition with AM630 enhances osteoclast activation. When JWH-133 is combined with vitamin D, its anti-osteoporotic action is reduced. GFD decreases osteoclast activity without restoring CB2 expression.

CB2 might be used as a molecular marker to forecast the likelihood of bone changes in CD patients, as well as a pharmaceutical target to minimize bone mass loss in individuals who require a direct intervention on bone metabolism in addition to the GFD.