Effect of Rubus coreanus extracts on diabetic osteoporosis by simultaneous regulation of osteoblasts and osteoclasts

Objective: Diabetes mellitus has been known to be associated with a high risk of osteoporosis. Rubus coreanus Miquel, a traditional Asian herbal medicine, has various uses, such as antiobesity and antiosteoporosis treatment, among others. We investigated the effect of R. coreanus extracts on diabetic osteoporosis. Methods: Rats were not treated, or treated with streptozotocin or R. coreanus, or ovariectomized, in various combinations. After 6 weeks of treatment, the rats were killed, and serum biochemistry, histopathology, immunohistochemistry, and semiquantitative reverse transcription polymerase chain reaction were performed. In addition, in vitro studies were performed in MC3T3-E1 and RAW 264.7 cells. Results: Rats treated using R. coreanus showed significant improvement in trabecular bone histopathology. Increased expression of osteocalcin was observed in rats treated with streptozotocin and R. coreanus, whether ovariectomized or not. In addition, the expression levels of cannabinoid receptors 1 and 2 and receptor activator for nuclear factor kappa beta ligand were increased in rats that were ovariectomized and treated with streptozotocin and R. coreanus but decreased in those treated with streptozotocin and R. coreanus alone. These results indicate that the antiosteoporotic effect of R. coreanus in postmenopausal diabetic osteoporosis is attributable to the cannabinoid receptor-dependent maximal up-regulation of osteoblastogenesis. Conclusions: The present study shows that R. coreanus may rescue diabetic osteoporotic bone loss by simultaneous alteration of activation in osteoblasts and osteoclasts. Furthermore, these effects may be partially influenced by the up-regulation of the endocannabinoid system. In conclusion, dietary R. coreanus may be of use in improving the conditions of diabetic osteoporosis.