TY - JOUR
T1 - 3,3′-Diindolylmethane attenuates experimental arthritis and osteoclastogenesis
AU - Dong, Lei
AU - Xia, Suhua
AU - Gao, Fengbo
AU - Zhang, Dachuan
AU - Chen, Jiangning
AU - Zhang, Junfeng
N1 - Funding Information:
This work was supported by National Natural Science Foundation of China ( 50673041 , 30771036 and BK2007144 ), National Basic Research Foundation of China ( 973 Program 2006CB503909 , 2004CB518603 ), Key Program for Science and Technology Research from Chinese Ministry of Education ( 01005 ), the Chinese National Programs for High Technology Research and Development ( 863 Program 2006AA02Z177 ), National Pharmaceutical Creation Program ( 2009ZX09503-028 ), China Postdoctoral Science Foundation 20080431077 and 200801364 .
PY - 2010/3/1
Y1 - 2010/3/1
N2 - 3,3′-Diindolylmethane (DIM) is a natural compound formed during the autolysis of glucobrassicin present in Brassica food plants. This study aimed to investigate the therapeutic efficacies of DIM on experimental arthritis. The effects of DIM on experimental arthritis were examined on a rat model of adjuvant-induced arthritis (AIA), with daily AIA paw swelling observation and histological/radiographic analysis. To elucidate the possible mechanisms of its action, serum cytokine levels as well as the expression of receptor activator for nuclear factor κ B ligand (RANKL) in infected tissues were subsequently analyzed. The impact of DIM on osteoclastogenesis was further investigated on a mouse model of endotoxin-induced bone resorption (EIBR) and in vitro cultures of fibroblast-like cells and osteoblasts, with RANKL expression being evaluated with great interest. The administration of DIM was demonstrated to attenuate AIA in animal models, as judged by clinical and histologic indices of inflammation and tissue damage. On the one hand, DIM could reduce the expression of several inflammatory cytokines, which was, however, not adequate to prevent the development of the arthritis. On the other hand, DIM was shown to effectively inhibit the expression of RANKL, leading to the blockade of osteoclastogenesis and consequently an alleviation of experimental arthritis. Further in vitro and in vivo studies confirmed the inhibition of RANKL by DIM. DIM has shown anti-arthritis activity in animal models via inhibiting the expression of RANKL, and thus may offer potential treatments for arthritis and associated disorders.
AB - 3,3′-Diindolylmethane (DIM) is a natural compound formed during the autolysis of glucobrassicin present in Brassica food plants. This study aimed to investigate the therapeutic efficacies of DIM on experimental arthritis. The effects of DIM on experimental arthritis were examined on a rat model of adjuvant-induced arthritis (AIA), with daily AIA paw swelling observation and histological/radiographic analysis. To elucidate the possible mechanisms of its action, serum cytokine levels as well as the expression of receptor activator for nuclear factor κ B ligand (RANKL) in infected tissues were subsequently analyzed. The impact of DIM on osteoclastogenesis was further investigated on a mouse model of endotoxin-induced bone resorption (EIBR) and in vitro cultures of fibroblast-like cells and osteoblasts, with RANKL expression being evaluated with great interest. The administration of DIM was demonstrated to attenuate AIA in animal models, as judged by clinical and histologic indices of inflammation and tissue damage. On the one hand, DIM could reduce the expression of several inflammatory cytokines, which was, however, not adequate to prevent the development of the arthritis. On the other hand, DIM was shown to effectively inhibit the expression of RANKL, leading to the blockade of osteoclastogenesis and consequently an alleviation of experimental arthritis. Further in vitro and in vivo studies confirmed the inhibition of RANKL by DIM. DIM has shown anti-arthritis activity in animal models via inhibiting the expression of RANKL, and thus may offer potential treatments for arthritis and associated disorders.
KW - 3,3′-Diindolylmethane
KW - Arthritis
KW - Osteoclastogenesis
KW - RANKL
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U2 - 10.1016/j.bcp.2009.10.010
DO - 10.1016/j.bcp.2009.10.010
M3 - Article
C2 - 19854159
AN - SCOPUS:71849091508
SN - 0006-2952
VL - 79
SP - 715
EP - 721
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 5
ER -