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BMC Musculoskeletal Disorders
Published in: BMC Musculoskeletal Disorders 1/2020

01-12-2020 | Osteoporosis | Research article

Polyphyllin VII attenuated RANKL-induced osteoclast differentiation via inhibiting of TRAF6/c-Src/PI3K pathway and ROS production

Authors: Long Zhou, Hanyi Song, Yiqi Zhang, Zhaozhou Ren, Minghe Li, Qin Fu

Published in: BMC Musculoskeletal Disorders | Issue 1/2020

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Abstract

Background

Osteoporosis is a worldwide severe bone disease. This study aimed to evaluate the effect of polyphyllin VII on the genesis of osteoclasts from bone marrow macrophages (BMMs) and its potentiality as a therapeutic drug for osteoporosis.

Methods

BMMs were induced to differentiate into osteoclasts by RANKL and M-CSF. The cells were then treated with various concentrations of polyphyllin VII. Intracellular reactive oxygen species (ROS) measurement assay, resorption pit formation assay, tartrate-resistant acid phosphatase (TRAP) staining and TRAP activity assessment, cell viability assay, active GTPase pull-down assay, immunofluorescent staining, immunoblotting, and RT-PCR were performed.

Results

RANKL + M-CSF significantly increased TRAP activity, number of osteoclasts, number and area of lacunae, intracellular content of ROS, protein levels of Nox1, TRAF6, c-Src and p-PI3K, as well as the content of activated GTP-Rac1, which were significantly blocked by polyphyllin VII in a concentration-dependent manner.

Conclusion

These findings suggested that polyphyllin VII inhibited differentiation of BMMs into osteoclasts through suppressing ROS synthesis, which was modulated by TRAF6–cSrc–PI3k signal transduction pathway including GTP-Rac1 and Nox1. Polyphyllin VII could be a therapeutic drug for osteoporosis.
Literature
1.
Hernlund E, Svedbom A, Ivergard M, Compston J, Cooper C, Stenmark J, et al. Osteoporosis in the European Union: medical management, epidemiology and economic burden. A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos. 2013;8:136.CrossRef
2.
Dawson-Hughes B, Looker AC, Tosteson AN, Johansson H, Kanis JA, Melton LJ 3rd. The potential impact of the National Osteoporosis Foundation guidance on treatment eligibility in the USA: an update in NHANES 2005-2008. Osteoporos Int. 2012;23(3):811–20.CrossRef
3.
Cummings SR, Melton LJ. Epidemiology and outcomes of osteoporotic fractures. Lancet. 2002;359(9319):1761–7.CrossRef
4.
Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King A, Tosteson A. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J Bone Miner Res. 2007;22(3):465–75.CrossRef
5.
Jin H, Dai J, Chen X, Liu J, Zhong D, Gu Y, et al. Pulmonary toxicity and metabolic activation of dauricine in CD-1 mice. J Pharmacol Exp Ther. 2010;332(3):738–46.CrossRef
6.
Anastasilakis AD, Toulis KA, Polyzos SA, Anastasilakis CD, Makras P. Long-term treatment of osteoporosis: safety and efficacy appraisal of denosumab. Ther Clin Risk Manag. 2012;8:295–306.CrossRef
7.
Finaud J, Lac G, Filaire E. Oxidative stress : relationship with exercise and training. Sports Med. 2006;36(4):327–58.CrossRef
8.
Wauquier F, Leotoing L, Coxam V, Guicheux J, Wittrant Y. Oxidative stress in bone remodelling and disease. Trends Mol Med. 2009;15(10):468–77.CrossRef
9.
Manolagas SC. From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis. Endocr Rev. 2010;31(3):266–300.CrossRef
10.
Callaway DA, Jiang JX. Reactive oxygen species and oxidative stress in osteoclastogenesis, skeletal aging and bone diseases. J Bone Miner Metab. 2015;33(4):359–70.CrossRef
11.
Sakai E, Shimada-Sugawara M, Yamaguchi Y, Sakamoto H, Fumimoto R, Fukuma Y, et al. Fisetin inhibits osteoclastogenesis through prevention of RANKL-induced ROS production by Nrf2-mediated up-regulation of phase II antioxidant enzymes. J Pharmacol Sci. 2013;121(4):288–98.CrossRef
12.
Kong X, Wu W, Yang Y, Wan H, Li X, Zhong M, et al. Total saponin from Anemone flaccida Fr. Schmidt abrogates osteoclast differentiation and bone resorption via the inhibition of RANKL-induced NF-kappaB, JNK and p38 MAPKs activation. J Transl Med. 2015;13:91.CrossRef
13.
Lee SH, Kim JK, Jang HD. Genistein inhibits osteoclastic differentiation of RAW 264.7 cells via regulation of ROS production and scavenging. Int J Mol Sci. 2014;15(6):10605–21.CrossRef
14.
Lee SH, Jang HD. Scoparone attenuates RANKL-induced osteoclastic differentiation through controlling reactive oxygen species production and scavenging. Exp Cell Res. 2015;331(2):267–77.CrossRef
15.
Tan EM, Li L, Indran IR, Chew N, Yong EL. TRAF6 mediates suppression of Osteoclastogenesis and prevention of Ovariectomy-induced bone loss by a novel Prenylflavonoid. J Bone Miner Res. 2017;32(4):846–60.CrossRef
16.
Yao N, Ren K, Wang Y, Jin Q, Lu X, Lu Y, et al. Paris polyphylla suppresses proliferation and Vasculogenic mimicry of human osteosarcoma cells and inhibits tumor growth in vivo. Am J Chin Med. 2017;45(3):575–98.CrossRef
17.
Li ZH, Wan JY, Wang GQ, Zhao FG, Wen JH. Identification of compounds from Paris polyphylla (ChongLou) active against Dactylogyrus intermedius. Parasitology. 2013;140(8):952–8.CrossRef
18.
He DX, Li GH, Gu XT, Zhang L, Mao AQ, Wei J, et al. A new agent developed by biotransformation of polyphyllin VII inhibits chemoresistance in breast cancer. Oncotarget. 2016;7(22):31814–24.PubMed
19.
Zhang C, Jia X, Bao J, Chen S, Wang K, Zhang Y, et al. Polyphyllin VII induces apoptosis in HepG2 cells through ROS-mediated mitochondrial dysfunction and MAPK pathways. BMC Complement Altern Med. 2016;16:58.CrossRef
20.
Zhang C, Jia X, Wang K, Bao J, Li P, Chen M, et al. Polyphyllin VII induces an Autophagic cell death by activation of the JNK pathway and inhibition of PI3K/AKT/mTOR pathway in HepG2 cells. PLoS One. 2016;11(1):e0147405.CrossRef
21.
Chen J, Wang B, Zhang J, Yang R, Fan L. Establishment of nude mouse model with ovarian carcinomaand the effect of Paris Phyllin VII combined with silica nano complex on the inhibition and the antioxidant ability of ovarian carcinoma in nude mice. Zhonghua Yi Xue Za Zhi. 2015;95(29):2393–5.PubMed
22.
Kim MH, Ryu SY, Choi JS, Min YK, Kim SH. Saurolactam inhibits osteoclast differentiation and stimulates apoptosis of mature osteoclasts. J Cell Physiol. 2009;221(3):618–28.CrossRef
23.
Lee NK, Choi YG, Baik JY, Han SY, Jeong DW, Bae YS, et al. A crucial role for reactive oxygen species in RANKL-induced osteoclast differentiation. Blood. 2005;106(3):852–9.CrossRef
24.
Sasaki H, Yamamoto H, Tominaga K, Masuda K, Kawai T, Teshima-Kondo S, et al. NADPH oxidase-derived reactive oxygen species are essential for differentiation of a mouse macrophage cell line (RAW264.7) into osteoclasts. J Med Investig. 2009;56(1–2):33–41.CrossRef
25.
Park HS, Lee SH, Park D, Lee JS, Ryu SH, Lee WJ, et al. Sequential activation of phosphatidylinositol 3-kinase, beta pix, Rac1, and Nox1 in growth factor-induced production of H2O2. Mol Cell Biol. 2004;24(10):4384–94.CrossRef
26.
Boudot C, Saidak Z, Boulanouar AK, Petit L, Gouilleux F, Massy Z, et al. Implication of the calcium sensing receptor and the Phosphoinositide 3-kinase/Akt pathway in the extracellular calcium-mediated migration of RAW 264.7 osteoclast precursor cells. Bone. 2010;46(5):1416–23.CrossRef
27.
Asagiri M, Sato K, Usami T, Ochi S, Nishina H, Yoshida H, et al. Autoamplification of NFATc1 expression determines its essential role in bone homeostasis. J Exp Med. 2005;202(9):1261–9.CrossRef
28.
Hsu H, Lacey DL, Dunstan CR, Solovyev I, Colombero A, Timms E, et al. Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Proc Natl Acad Sci U S A. 1999;96(7):3540–5.CrossRef
29.
Takayanagi H. Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems. Nat Rev Immunol. 2007;7(4):292–304.CrossRef
Metadata
Title
Polyphyllin VII attenuated RANKL-induced osteoclast differentiation via inhibiting of TRAF6/c-Src/PI3K pathway and ROS production
Authors
Long Zhou
Hanyi Song
Yiqi Zhang
Zhaozhou Ren
Minghe Li
Qin Fu
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2020
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/s12891-020-3077-z

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