PGE2 is mainly produced by cyclooxygenase-2 (COX-2) in osteoblasts and acts as a potent stimulator of bone resorption (52) and (53). IL-1 is known to induce PGE2 production by osteoblasts and RANKL expression on their surface. Recently, several group studies revealed that DIM reduces inflammation (19) and (54). Kim et al. investigated DIM inhibition of the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced increases in the expression
of COX-2, inducible nitric oxide synthase, chemokine (C-X-C motif) ligand (CXCL) 5, and IL-6 in mouse skin (54). DIM also inhibited NFκB DNA binding activity, the nuclear translocation of p65, and the degradation of inhibitor of κBα in TPA-stimulated mouse skin Doxorubicin mouse (54). Dong et al. found that DIM attenuates experimental arthritis by reducing the expression of several inflammatory cytokines including tumor necrosis factor-alpha Bioactive Compound Library (TNF-α), IL-1 and nitric oxide (19). Moreover, Kim et al. showed that DIM attenuates colonic inflammation and tumorigenesis with a significant reduction in colonic myeloperoxidase activity and production of PGE2, nitric oxide, and pro-inflammatory cytokines (55). This series of evidence
enables us to begin to evaluate whether DIM could potentially prevent bone loss in women with postmenopausal osteoporosis. To enhance bone loss in the mice, an OVX model with diminished estrogen producing capacity was utilized. This model has been widely used in research
to approximate the type of condition that can be an etiological factor in pathological bone loss in postmenopausal women and which could possibly lead to a condition of osteoporosis. Bone phenotypic analyses in this mouse model showed that DIM treatment could effectively prevent OVX-induced bone loss by suppressing osteoclastic bone resorption (Fig. 3 and Fig. 4). Our results suggest that DIM may be of value in the prevention and treatment of postmenopausal osteoporosis. A limitation of this study is that the validation of function of DIM in bone metabolism under pathological conditions was performed using only an OVX mouse model. Future 17-DMAG (Alvespimycin) HCl studies are required to determine whether DIM would likewise protect against bone loss in other mouse models with conditions such as lipopolysaccharide-induced inflammatory bone loss. In addition, precise molecular mechanisms still remain elusive, even though our study directly elucidated that DIM plays a significant role in the control of bone mass under physiological and pathological conditions, as determined by the use of DEXA, μCT, and bone histomorphometric analyses. Further studies are needed to more profoundly comprehend the detailed molecular basis of the function of DIM in bone metabolism, such as examining whether the function of DIM is related with AhR in osteoclasts using osteoclast-specific AhR deletion mice.