title: Eriodicyol inhibits osteoclast differentiation and ovariectomy-induced bone loss in vivo.
abstract: Osteoclasts are responsible for bone erosion in diseases such as osteoporosis and rheumatoid arthritis. In the present study, we investigate the effects of eriodictyol, a flavonoid found naturally in citrus fruits, on the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation using mouse bone marrow macrophages (BMMs). Eriodictyol inhibited RANKL-induced osteoclast formation in a dose-dependent manner without cytotoxicity. In addition, eriodictyol suppressed bone resorption activity of differentiated osteoclasts. The inhibitory effect of eriodictyol was associated with impaired activation of multiple signaling events downstream of RANK, including extracellular signal-regulated kinase, p38, and c-Jun terminal kinase phosphorylation, followed by decreased nuclear factor of activated T cells (NFAT)c1 expression. Ectopic overexpression of a constitutively active form of NFATc1 completely rescued the anti-osteoclastogenic effect of eriodictyol, suggesting that the anti-osteoclastogenic effect was mainly attributed to the reduction in NFATc1 expression. Consistent with the in vitro anti-osteoclastogenic effect, eriodictyol suppressed lipopolysaccharide-induced osteoclast formation in the calvarial model and ovariectomy-induced bone loss in vivo. Taken together, our data demonstrate that eriodictyol is a new therapeutic agent with the potential to prevent bone destructive diseases by reducing both osteoclast differentiation and function.
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Cheongpa-ro 47-gil 100, Yongsan-ku, Seoul 140-742, Republic of Korea.
authors.forename: Juhyun
authors.initials: J
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Cheongpa-ro 47-gil 100, Yongsan-ku, Seoul 140-742, Republic of Korea.
authors.forename: A Long Sae Mi
authors.initials: AL
authors.lastname: Noh
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Cheongpa-ro 47-gil 100, Yongsan-ku, Seoul 140-742, Republic of Korea.
authors.forename: Ting
authors.initials: T
authors.lastname: Zheng
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Cheongpa-ro 47-gil 100, Yongsan-ku, Seoul 140-742, Republic of Korea.
authors.forename: Ju-hee
authors.initials: JH
authors.lastname: Kang
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Cheongpa-ro 47-gil 100, Yongsan-ku, Seoul 140-742, Republic of Korea. Electronic address: myim@sm.ac.kr.
authors.forename: Mijung
authors.initials: M
authors.lastname: Yim
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001862:Bone Resorption / Q000517:prevention & control*; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology*; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D010052:Ovariectomy; D053245:RANK Ligand / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D044950:Flavanones; D005419:Flavonoids; D053245:RANK Ligand; C007619:eriodictyol
keywords: Bone loss; Eriodictyol; Osteoclast; RANKL