title: Magnolol Inhibits RANKL-induced osteoclast differentiation of raw 264.7 macrophages through heme oxygenase-1-dependent inhibition of NFATc1 expression.
abstract: Magnolol (1) isolated from Magnolia officinalis exhibits many beneficial effects such as anti-inflammatory and antioxidant activity. The aim of this study was to evaluate the effects of magnolol (1) on RANKL-induced osteoclast differentiation and investigate the underlying molecular mechanisms. Treatment with magnolol (1) significantly inhibited osteoclast differentiation of RAW 264.7 macrophages and bone-resorbing activity of osteoclasts in the RANKL-induced system. Moreover, RANKL-activated JNK/ERK/AP-1 and NF-κB signaling, ROS formation, and NFATc1 activation were attenuated by magnolol (1). A novel finding of this study is that magnolol (1) can increase heme oxygenase-1 (HO-1) expression and Nrf2 activation in RANKL-stimulated cells. Blocking HO-1 activity with tin protoporphyrin IX markedly reversed magnolol (1)-mediated inhibition of osteoclast differentiation, NFATc1 nuclear translocation, and MMP-9 activity, suggesting that HO-1 contributes to the attenuation of NFATc1-mediated osteoclastogenesis by magnolol (1). Therefore, the inhibitory effect of magnolol (1) on osteoclast differentiation is due to inhibition of MAPK/c-fos/AP-1 and NF-κB signaling as well as ROS production and up-regulation of HO-1 expression, which ultimately suppresses NFATc1 induction. These findings indicate that magnolol (1) may have potential to treat bone diseases associated with excessive osteoclastogenesis.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center , Taipei, Taiwan.
authors.forename: Sheng-Hua
authors.initials: SH
authors.lastname: Lu
authors.forename: Tso-Hsiao
authors.initials: TH
authors.lastname: Chen
authors.forename: Tz-Chong
authors.initials: TC
authors.lastname: Chou
mesh_terms: D001713:Biphenyl Compounds / Q000737:chemistry / Q000494:pharmacology*; D001847:Bone Diseases / Q000188:drug therapy; D001854:Bone Marrow Cells / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D017705:Lignans / Q000737:chemistry / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects*; D031566:Magnolia / Q000737:chemistry; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D010010:Osteoclasts / Q000187:drug effects*; D053245:RANK Ligand / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000187:drug effects; D014157:Transcription Factors; D015854:Up-Regulation
chemical_list: D001713:Biphenyl Compounds; D017705:Lignans; D016328:NF-kappa B; D053245:RANK Ligand; D018808:Transcription Factor AP-1; D014157:Transcription Factors; C005498:magnolol; D051547:Heme Oxygenase-1