caa a22 4500 606235671 CHVBK 20210128101243.0 cr unu---uuuuu 210128e20150901xx s 000 0 eng 10.1007/s11010-015-2466-3 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2466-3 Punicalagin attenuates osteoclast differentiation by impairing NFATc1 expression and blocking Akt- and JNK-dependent pathways [Elektronische Daten] [Mayumi Iwatake, Kuniaki Okamoto, Takashi Tanaka, Takayuki Tsukuba] Punicalagin is a bioactive polyphenol that is classified as an ellagitannin. Although punicalagin has been shown to have various pharmacological effects, such as anti-oxidative, anti-inflammatory, and anti-tumor effects, no studies have reported the effects of punicalagin on osteoclasts (OCLs). In this study, we investigated the effects of punicalagin on OCL differentiation by receptor activator of nuclear factor kappa-B ligand in the murine monocytic RAW-D cell line and bone marrow-derived macrophages (BMMs). Treatment with punicalagin significantly inhibited OCL formation from RAW-D cells and BMMs and prevented bone resorption of BMM-derived OCLs. Moreover, punicalagin impaired multinucleation and actin-ring formation in OCLs, and decreased the protein levels of nuclear factor of activated T cells cytoplasmic-1 (NFATc1), which is a master regulator of OCL differentiation, and concomitantly reduced the expression levels of Src and cathepsin K, which are transcriptionally regulated by NFATc1. The effects of punicalagin on intracellular signaling during the OCL differentiation of BMMs indicated that punicalagin-treated OCLs displayed markedly reduced phosphorylation of Jun N-terminal kinase and Akt, and partially impaired phosphorylation of extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, and inhibitor of nuclear factor kappa-B alpha compared with untreated OCLs. Thus, punicalagin may affect bone metabolism by inhibiting OCL differentiation. Springer Science+Business Media New York, 2015 Osteoclasts nationallicence Punicalagin nationallicence NFATc1 nationallicence OCLs : Osteoclasts nationallicence RANKL : Receptor activator of nuclear factor kappa-B ligand nationallicence BMMs : Bone marrow-derived macrophages nationallicence NFATc1 : Nuclear factor of activated T cells cytoplasmic-1 nationallicence IκBα : Nuclear factor kappa-B alpha nationallicence TRAP : Tartrate-resistant acid phosphatase nationallicence M-CSF : Macrophage colony-stimulating factor nationallicence NF-κB : Nuclear factor kappa-B nationallicence PI3K : Phosphatidylinositol 3-kinase nationallicence JNK : Jun N-terminal kinase nationallicence Erk : Extracellular signal-regulated kinase nationallicence MAPK : Mitogen-activated protein kinase nationallicence HO-1 : Heme oxygenase-1 nationallicence NFAT : Nuclear factor of activated T cells nationallicence Abs : Antibodies nationallicence SD : Standard deviations nationallicence PMSF : Phenylmethylsulfonyl fluoride nationallicence TBS-T : Tris buffered saline with 0.1% Tween 20 nationallicence Iwatake Mayumi Division of Dental Pharmacology, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-7-1, 852-8588, Nagasaki, Japan aut Okamoto Kuniaki Division of Dental Pharmacology, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-7-1, 852-8588, Nagasaki, Japan aut Tanaka Takashi Division of Natural Product Chemistry, Nagasaki University Graduate School of Biomedical Sciences, Bunkyo, 1-14, 852-8521, Nagasaki, Japan aut Tsukuba Takayuki Division of Dental Pharmacology, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-7-1, 852-8588, Nagasaki, Japan aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 407/1-2(2015-09-01), 161-172 0300-8177 407:1-2<161 2015 407 11010 https://doi.org/10.1007/s11010-015-2466-3 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2466-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Iwatake Mayumi Division of Dental Pharmacology, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-7-1, 852-8588, Nagasaki, Japan aut NATIONALLICENCE 700 1- Okamoto Kuniaki Division of Dental Pharmacology, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-7-1, 852-8588, Nagasaki, Japan aut NATIONALLICENCE 700 1- Tanaka Takashi Division of Natural Product Chemistry, Nagasaki University Graduate School of Biomedical Sciences, Bunkyo, 1-14, 852-8521, Nagasaki, Japan aut NATIONALLICENCE 700 1- Tsukuba Takayuki Division of Dental Pharmacology, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-7-1, 852-8588, Nagasaki, Japan aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 407/1-2(2015-09-01), 161-172 0300-8177 407:1-2<161 2015 407 11010