Eriodicyol inhibits osteoclast differentiation and ovariectomy-induced bone loss in vivo

• Published in: Experimental cell research 2015-12, Vol.339 (2), p.380-388
• Main Authors: Lee, Juhyun, Noh, A Long Sae Mi, Zheng, Ting, Kang, Ju-hee, Yim, Mijung
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Animals; Bone density; Bone Density - drug effects; Bone loss; BONE MARROW; Bone Resorption - prevention & control; Cell Differentiation - drug effects; Cells, Cultured; Cellular biology; CITRUS; Dose-Response Relationship, Drug; DOSES; DRUGS; Eriodictyol; Flavanones - chemistry; Flavanones - pharmacology; FLAVONOIDS; Flavonoids - chemistry; Flavonoids - pharmacology; FRUITS; IN VITRO; IN VIVO; LIGANDS; LIPOPOLYSACCHARIDES; MACROPHAGES; MICE; Mice, Inbred ICR; Osteoclast; Osteoclasts - cytology; Osteoclasts - drug effects; OSTEOPOROSIS; Ovariectomy; PHOSPHORUS 38; PHOSPHORYLATION; PHOSPHOTRANSFERASES; Phytochemicals; RANK Ligand - antagonists & inhibitors; RANK Ligand - pharmacology; RANKL; RECEPTORS; REDUCTION; RHEUMATIC DISEASES; Signal transduction; SIGNALS; SKELETON; Structure-Activity Relationship; TOXICITY
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2015.10.001

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. •Eriodictyol from citrus fruits inhibited RANKL-induced osteoclast.•Eriodictyol suppressed bone resorption activity of mature osteoclasts.•Eriodictyol impaired MAPK–NFATc1 signaling pathways in osteoclasts.•Eriodictyol decreased LPS-induced osteoclast formation in vivo.•Eriodictyol prevented ovariectomy-induced bone loss in vivo.