Purslane Suppresses Osteoclast Differentiation and Bone Resorbing Activity via Inhibition of Akt/GSK3β-c-Fos-NFATc1 Signaling in Vitro and Prevents Lipopolysaccharide-Induced Bone Loss in Vivo

被引:37
作者
Kim, Ju-Young [1 ]
Oh, Hyun Mee [2 ]
Kwak, Sung Chul [3 ]
Cheon, Yoon-Hee [4 ,5 ,6 ]
Lee, Myeung Su [7 ]
Rho, Mun Chual [2 ]
Oh, Jaemin [1 ,4 ,5 ,6 ]
机构
[1] Wonkwang Univ, Imaging Sci Lung & Bone Dis Res Ctr, Iksan 570749, Jeonbuk, South Korea
[2] Korea Res Inst Biosci & Biotechnol, Biomat Res Inst, Bioind Proc Res Ctr, Jeongeup 580185, Jeonbuk, South Korea
[3] NeuMed Inc, KISTEM, Seoul 130701, South Korea
[4] Wonkwang Univ, Sch Med, Dept Anat, Iksan 570749, Jeonbuk, South Korea
[5] Wonkwang Univ, Grad Sch, Program BK21plus, Iksan 570749, Jeonbuk, South Korea
[6] Wonkwang Univ, Grad Sch, Dept Smart Life Care Convergence, Iksan 570749, Jeonbuk, South Korea
[7] Wonkwang Univ, Dept Internal Med, Div Rheumatol, Iksan 570749, Jeonbuk, South Korea
关键词
purslane (Portulaca oleracea); osteoclast; bone loss; osteoporosis; natural medicine; KEY REGULATOR; C-FOS; PROTEIN; RANKL; RECEPTOR; LIGAND;
D O I
10.1248/bpb.b14-00567
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Purslane (Portulaca oleracea L.) is popular as a potherb in many areas of Europe, Asia, and the Mediterranean region and is widely distributed around the globe. It has a wide range of pharmacological effects, such as antibacterial, anti-aging, anti-inflammatory, and anti-oxidative properties. Although the extract of purslane has numerous beneficial pharmacological effects, its effect on osteoclasts remains unknown. We aimed to investigate the anti-osteoclastogenic activity in vitro and in vivo and to elucidate the underlying mechanism. The effect of purslane on the differentiation and function of bone marrow-derived macrophages (BMMs) into osteoclasts was examined using a phenotype assay such as tartrate-resistant acid phosphatase (TRAP) staining, F-actin staining, and pit assay and followed by confirmation by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. To address the effect of purslane in vivo, the inflammatory, lipopolysaccharide (LPS)-induced osteolysis mouse model was chosen. Bone volume and bone microarchitecture were evaluated by microcomputed tomography and histologic analysis. Purslane inhibited receptor activator of nuclear factor-kappa B ligand (RANKL)-stimulated osteoclast differentiation accompanied by inhibition of Akt/glycogen synthase kinase 3 beta (GSK3 beta) signaling, which could underlie purslane-induced downregulation of c-Fos and nuclear factor of activated T cells 1 (NFATc1) expression levels, transcription factors that regulate osteoclast-specific genes, as well as osteoclast fusion and resorption-related molecules. Moreover, in vivo studies further verified the bone protection activity of purslane in the LPS-induced osteolysis animal model. Purslane could exhibit its anti-osteoclastogenic activity by inhibiting Akt/GSK3 beta-c-Fos-NFATc1 signaling cascades. Therefore, purslane is a potential natural medicine for the treatment of osteoclast-related diseases.
引用
收藏
页码:66 / 74
页数:9
相关论文
共 26 条
[1]   Transgenic mice overexpressing tartrate-resistant acid phosphatase exhibit an increased rate of bone turnover [J].
Angel, NZ ;
Walsh, N ;
Forwood, MR ;
Ostrowski, MC ;
Cassady, AI ;
Hume, DA .
JOURNAL OF BONE AND MINERAL RESEARCH, 2000, 15 (01) :103-110
[2]   Osteoclast differentiation and activation [J].
Boyle, WJ ;
Simonet, WS ;
Lacey, DL .
NATURE, 2003, 423 (6937) :337-342
[3]   Critical Role of AKT Protein in Myeloma-induced Osteoclast Formation and Osteolysis [J].
Cao, Huiling ;
Zhu, Ke ;
Qiu, Lugui ;
Li, Shuai ;
Niu, Hanjie ;
Hao, Mu ;
Yang, Shengyong ;
Zhao, Zhongfang ;
Lai, Yumei ;
Anderson, Judith L. ;
Fan, Jie ;
Im, Hee-Jeong ;
Chen, Di ;
Roodman, G. David ;
Xiao, Guozhi .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2013, 288 (42) :30399-30410
[4]   The analgesic and anti-inflammatory effects of Portulaca oleracea L. subsp sativa (Haw.) Celak [J].
Chan, K ;
Islam, MW ;
Kamil, M ;
Radhakrishnan, R ;
Zakaria, MNM ;
Habibullah, M ;
Attas, A .
JOURNAL OF ETHNOPHARMACOLOGY, 2000, 73 (03) :445-451
[5]   Matrix metalloproteinases (MMP) and cathepsin K contribute differently to osteoclastic activities [J].
Delaissé, JM ;
Andersen, TL ;
Engsig, MT ;
Henriksen, K ;
Troen, T ;
Blavier, L .
MICROSCOPY RESEARCH AND TECHNIQUE, 2003, 61 (06) :504-513
[6]   Phosphatidylinositol 3-kinase coordinately activates the MEK/ERK and AKT/NFκB pathways to maintain osteoclast survival [J].
Gingery, A ;
Bradley, E ;
Shaw, A ;
Oursler, MJ .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2003, 89 (01) :165-179
[7]   C-FOS - A KEY REGULATOR OF OSTEOCLAST-MACROPHAGE LINEAGE DETERMINATION AND BONE REMODELING [J].
GRIGORIADIS, AE ;
WANG, ZQ ;
CECCHINI, MG ;
HOFSTETTER, W ;
FELIX, R ;
FLEISCH, HA ;
WAGNER, EF .
SCIENCE, 1994, 266 (5184) :443-448
[8]   Control of osteoblast function and regulation of bone mass [J].
Harada, S ;
Rodan, GA .
NATURE, 2003, 423 (6937) :349-355
[9]   Podosome and sealing zone: Specificity of the osteoclast model [J].
Jurdic, P ;
Saltel, F ;
Chabadel, A ;
Destaing, O .
EUROPEAN JOURNAL OF CELL BIOLOGY, 2006, 85 (3-4) :195-202
[10]   NFATc1 induces osteoclast fusion via up-regulation of atp6v0d2 and the dendritic cell-specific transmembrane protein (DC-STAMP) [J].
Kim, Kabsun ;
Lee, Seoung-Hoon ;
Kim, Jung Ha ;
Choi, Yongwon ;
Kim, Nacksung .
MOLECULAR ENDOCRINOLOGY, 2008, 22 (01) :176-185