Collectively, our results showed a pivotal role of miR-187-3p/CNR2 axis in osteoblastic differentiation, indicating that miR-187-3p may serve as a promising target in the therapy of osteoporosis.
The objective of this study was to investigate the association of four single-nucleotide polymorphisms (SNPs) of the cannabinoid receptor 2 (<i>CNR2</i>) gene, gene-obesity interaction, and haplotype combination with osteoporosis (OP) susceptibility.
Additionally, analyses by haplotypes indicated that two haplotype blocks, containing rs4237 and rs2501431 respectively, in the CNR2 gene significantly associated with BMD and osteoporosis (both global permutation p < 0.001), and a risk haplotype (ATTT) in the block of rs3003336-rs2501431-rs2502992-rs2501432 had almost 4-fold increase in the cases.
Bone mass and turnover were normal in young mice with targeted inactivation of CB2 receptor (CB2(-/-)), but by 12 months of age, they had developed high-turnover osteoporosis with relative uncoupling of bone resorption from bone formation.
Genetic variants within the CNR2 gene encoding the cannabinoid receptor CB2 have been shown to be associated with osteoporosis and low bone mineral density (BMD) in case-control studies.
Taken together, the reports on cannabinoid receptors in mice and humans pave the way for the development of 1) diagnostic measures to identify osteoporosis-susceptible polymorphisms in CNR2, and 2) cannabinoid drugs to combat osteoporosis.
These results demonstrate a role for the peripherally expressed CB2 receptor in the etiology of osteoporosis and provide an interesting novel therapeutical target for this severe and common disease.
These results demonstrate a role for the peripherally expressed CB2 receptor in the etiology of osteoporosis and provide an interesting novel therapeutical target for this severe and common disease.