Sargachromanol G regulates the expression of osteoclastogenic factors in human osteoblast-like MG-63 cells.
Bone diseases are characterized by the presence of pro-inflammatory cytokines that regulate bone turnover. The receptor activator of NF-κB ligand (RANKL) is a soluble osteoblast-derived protein that induces bone resorption through osteoclast differentiation and activation. Sargachromanol G (SG) was isolated from the brown algae Sargassum siliquastrum; SG has anti-osteoclastogenic activity, but its mechanism of action and its active components remain largely unknown. In the present study, we investigated the anti-osteoclastogenic effects of SG on the expression of interleukin-1β (IL-1β)-induced osteoclastogenic factors (PGE(2), COX-2, IL-6, OPG, and RANKL) in the human osteoblast cell line MG-63. We also examined the role of the nuclear factor-κB (NF-κB) and the mitogen-activated protein kinase (MAPK) signaling pathways in IL-1β-stimulated MG-63 cells. SG dose-dependently inhibited the production of osteoclastogenic factors in MG-63 cells. SG also inhibited phosphorylation of MAPK (ERK1/2, p38, and JNK) and NF-κB (p65, p50, and IκB-α). These results suggest that the anti-osteoporotic effect of SG may be because of the modulation of osteoclastogenic factors via suppression of MAPK and NF-κB activation.
Department of Pharmacology, College of Medicine, Jeju National University, Jeju 690-756, Republic of Korea.
Weon-Jong
WJ
Yoon
Soo-Jin
SJ
Heo
Sang-Chul
SC
Han
Hye-Ja
HJ
Lee
Gyeoung-Jin
GJ
Kang
Eun-Jin
EJ
Yang
Sun-Soon
SS
Park
Hee-Kyoung
HK
Kang
Eun-Sook
ES
Yoo
D001578:Benzopyrans / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D020935:MAP Kinase Signaling System; D016328:NF-kappa B / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053244:Osteoprotegerin / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D015398:Signal Transduction
D001578:Benzopyrans; D015850:Interleukin-6; D016328:NF-kappa B; D053244:Osteoprotegerin; D053245:RANK Ligand; C505688:TNFSF11 protein, human; C577249:sargachromanol G; D051546:Cyclooxygenase 2; D015232:Dinoprostone