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BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2020

01-12-2020 | Osteoporosis | Research article

Chaenomelis fructus inhibits osteoclast differentiation by suppressing NFATc1 expression and prevents ovariectomy-induced osteoporosis

Authors: Minsun Kim, Ho-Seok Kim, Jae-Hyun Kim, Eun-Young Kim, Bina Lee, Sung Yub Lee, Jae-Yun Jun, Min Beom Kim, Youngjoo Sohn, Hyuk-Sang Jung

Published in: BMC Complementary Medicine and Therapies | Issue 1/2020

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Abstract

Background

Osteoporosis is related to the number and activity of osteoclasts. The goal of the present study was to demonstrate the effect of Chaenomelis Fructus (CF) on osteoclastogenesis and its mechanism of bone loss prevention in an OVX-induced osteoporosis model.

Methods

Osteoclasts were induced by RANKL in RAW 264.7 cells. TRAP assay was performed to measure the inhibitory effect of CF on osteoclast differentiation. Then, Expression of nuclear factor of activated T-cells (NFATc1), c-Fos which are essential transcription factors in osteoclastogenesis were detected using western blot and RT-PCR. The osteoclast-related markers were measured by RT-PCR. Moreover, the ability of CF to inhibit bone loss was researched by ovariectomized (OVX)-induced osteoporosis.

Results

Cell experiments showed that CF inhibited osteoclast differentiation and its function. Immunoblot analyses demonstrated that CF suppressed osteoclastogenesis through the NFATc1 and c-Fos signaling pathways. RT-PCR determined that CF inhibited osteoclast-related markers, such as tartrate-resistant acid phosphatase (TRAP), cathepsin K (CTK), osteoclast-associated immunoglobulin-like receptor (OSCAR), ATPase H+ Transporting V0 Subunit D2 (ATP6v0d2) and carbonic anhydrase II (CA2). In animal experiments, CF showed an inhibitory effect on bone density reduction through OVX. Hematoxylin and eosin (H&E) staining analysis data showed that CF inhibited OVX-induced trabecular area loss. TRAP staining and immunohistochemical staining analysis data showed that CF displayed an inhibitory effect on osteoclast differentiation through NFATc1 inhibition in femoral tissue.

Conclusion

Based on the results of in vivo and in vitro experiments, CF inhibited the RANKL-induced osteoclasts differentiation and its function and effectively ameliorated OVX-induced osteoporosis rats.
Appendix
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Literature
1.
Sozen T, Ozisik L, Basaran NC. An overview and management of osteoporosis. Eur J Rheumatol. 2017;4(1):46–56.PubMedCrossRef
2.
Heaney RP. Pathophysiology of osteoporosis. Endocrinol Metab Clin N Am. 1998;27(2):255–65.CrossRef
3.
Walsh MC, Kim N, Kadono Y, Rho J, Lee SY, Lorenzo J, Choi Y. Osteoimmunology: interplay between the immune system and bone metabolism. Annu Rev Immunol. 2006;24:33–63.PubMedCrossRef
4.
de Villiers TJ. The role of menopausal hormone therapy in the management of osteoporosis. Climacteric. 2015;18(Suppl 2):19–21.PubMedCrossRef
5.
Bar-Shavit Z. The osteoclast: a multinucleated, hematopoietic-origin, bone-resorbing osteoimmune cell. J Cell Biochem. 2007;102(5):1130–9.PubMedCrossRef
6.
7.
Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature. 2003;423(6937):337–42.PubMedCrossRef
8.
Grigoriadis AE, Wang ZQ, Cecchini MG, Hofstetter W, Felix R, Fleisch HA, Wagner EF. C-Fos: a key regulator of osteoclast-macrophage lineage determination and bone remodeling. Science. 1994;266(5184):443–8.PubMedCrossRef
9.
Zhao Q, Wang X, Liu Y, He A, Jia R. NFATc1: functions in osteoclasts. Int J Biochem Cell Biol. 2010;42(5):576–9.PubMedCrossRef
10.
David JP, Rincon M, Neff L, Horne WC, Baron R. Carbonic anhydrase II is an AP-1 target gene in osteoclasts. J Cell Physiol. 2001;188(1):89–97.PubMedCrossRef
11.
Fujisaki K, Tanabe N, Suzuki N, Kawato T, Takeichi O, Tsuzukibashi O, Makimura M, Ito K, Maeno M. Receptor activator of NF-kappaB ligand induces the expression of carbonic anhydrase II, cathepsin K, and matrix metalloproteinase-9 in osteoclast precursor RAW264.7 cells. Life Sci. 2007;80(14):1311–8.PubMedCrossRef
12.
13.
Giannakeas V, Cadarette SM, Ban JK, Lipscombe L, Narod SA, Kotsopoulos J. Denosumab and breast cancer risk in postmenopausal women: a population-based cohort study. Br J Cancer. 2018.
14.
15.
Persson I, Weiderpass E, Bergkvist L, Bergstrom R, Schairer C. Risks of breast and endometrial cancer after estrogen and estrogen-progestin replacement. CCC. 1999;10(4):253–60.PubMed
16.
Herbology Editorial Committee of Korean Medicine: Herbology. Younglimsa, Seoul, 2004 (In Korean).
17.
Chen Q, Wei W. Effects and mechanisms of glucosides of chaenomeles speciosa on collagen-induced arthritis in rats. Int Immunopharmacol. 2003;3(4):593–608.PubMedCrossRef
18.
Takayanagi H. Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems. Nat Rev Immunol. 2007;7(4):292–304.PubMedCrossRef
19.
Tanabe N, Maeno M, Suzuki N, Fujisaki K, Tanaka H, Ogiso B, Ito K. IL-1 alpha stimulates the formation of osteoclast-like cells by increasing M-CSF and PGE2 production and decreasing OPG production by osteoblasts. Life Sci. 2005;77(6):615–26.PubMedCrossRef
20.
Kalu DN. The ovariectomized rat model of postmenopausal bone loss. Bone Mineral. 1991;15(3):175–91.PubMedCrossRef
21.
Miao J, Zhao C, Li X, Chen X, Mao X, Huang H, Wang T, Gao W. Chemical composition and bioactivities of two common Chaenomeles fruits in China: Chaenomeles speciosa and Chaenomeles sinensis. J Food Sci. 2016;81(8):H2049–58.PubMedCrossRef
22.
Collin-Osdoby P, Yu X, Zheng H, Osdoby P. RANKL-mediated osteoclast formation from murine RAW 264.7 cells. Methods Mol Med. 2003;80:153–66.PubMed
23.
Hsu H, Lacey DL, Dunstan CR, Solovyev I, Colombero A, Timms E, Tan HL, Elliott G, Kelley MJ, Sarosi I, 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.PubMedPubMedCentralCrossRef
24.
Armstrong AP, Tometsko ME, Glaccum M, Sutherland CL, Cosman D, Dougall WC. A RANK/TRAF6-dependent signal transduction pathway is essential for osteoclast cytoskeletal organization and resorptive function. J Biol Chem. 2002;277(46):44347–56.PubMedCrossRef
25.
Soysa NS, Alles N. NF-kappaB functions in osteoclasts. Biochem Biophys Res Commun. 2009;378(1):1–5.PubMedCrossRef
26.
Kobayashi N, Kadono Y, Naito A, Matsumoto K, Yamamoto T, Tanaka S, Inoue J. Segregation of TRAF6-mediated signaling pathways clarifies its role in osteoclastogenesis. EMBO J. 2001;20(6):1271–80.PubMedPubMedCentralCrossRef
27.
Huang H, Chang EJ, Ryu J, Lee ZH, Lee Y, Kim HH. Induction of c-Fos and NFATc1 during RANKL-stimulated osteoclast differentiation is mediated by the p38 signaling pathway. Biochem Biophys Res Commun. 2006;351(1):99–105.PubMedCrossRef
28.
David JP, Sabapathy K, Hoffmann O, Idarraga MH, Wagner EF. JNK1 modulates osteoclastogenesis through both c-Jun phosphorylation-dependent and -independent mechanisms. J Cell Sci. 2002;115(Pt 22):4317–25.PubMedCrossRef
29.
30.
Kim JY, Cheon YH, Yoon KH, Lee MS, Oh J. Parthenolide inhibits osteoclast differentiation and bone resorbing activity by down-regulation of NFATc1 induction and c-Fos stability, during RANKL-mediated osteoclastogenesis. BMB Rep. 2014;47(8):451–6.PubMedPubMedCentralCrossRef
31.
Kang TH, Baek HY, Kim YC. Protective effect of jakyak-gamcho-tang extract and its constituents against t-BHP-induced oxidative damage in HT22 cells. Am J Chin Med. 2005;33(2):181–9.PubMedCrossRef
32.
Kim K, Lee SH, Ha Kim J, Choi Y, Kim N. NFATc1 induces osteoclast fusion via up-regulation of Atp6v0d2 and the dendritic cell-specific transmembrane protein (DC-STAMP). Mol Endocrinol. 2008;22(1):176–85.PubMedCrossRef
33.
Biskobing DM, Fan D, Fan X, Rubin J. Induction of carbonic anhydrase II expression in osteoclast progenitors requires physical contact with stromal cells. Endocrinology. 1997;138(11):4852–7.PubMedCrossRef
34.
Kim SB, Ahn B, Kim M, Ji HJ, Shin SK, Hong IP, Kim CY, Hwang BY, Lee MK. Effect of Cordyceps militaris extract and active constituents on metabolic parameters of obesity induced by high-fat diet in C58BL/6J mice. J Ethnopharmacol. 2014;151(1):478–84.PubMedCrossRef
35.
Kim JH, Kim K, Jin HM, Youn BU, Song I, Choi HS, Kim N. Upstream stimulatory factors regulate OSCAR gene expression in RANKL-mediated osteoclast differentiation. J Mol Biol. 2008;383(3):502–11.PubMedCrossRef
36.
Lee SH, Rho J, Jeong D, Sul JY, Kim T, Kim N, Kang JS, Miyamoto T, Suda T, Lee SK, et al. V-ATPase V0 subunit d2-deficient mice exhibit impaired osteoclast fusion and increased bone formation. Nat Med. 2006;12(12):1403–9.PubMedCrossRef
37.
Henriksen K, Tanko LB, Qvist P, Delmas PD, Christiansen C, Karsdal MA. Assessment of osteoclast number and function: application in the development of new and improved treatment modalities for bone diseases. Osteoporos Int. 2007;18(5):681–5.PubMedCrossRef
38.
Barlet JP, Coxam V, Davicco MJ, Gaumet N. Animal models of post-menopausal osteoporosis. Reprod Nutr Dev. 1994;34(3):221–36.PubMedCrossRef
39.
Miyazaki T, Matsunaga T, Miyazaki S, Hokari S, Komoda T. Changes in receptor activator of nuclear factor-kappaB, and its ligand, osteoprotegerin, bone-type alkaline phosphatase, and tartrate-resistant acid phosphatase in ovariectomized rats. J Cell Biochem. 2004;93(3):503–12.PubMedCrossRef
40.
41.
Ozer J, Ratner M, Shaw M, Bailey W, Schomaker S. The current state of serum biomarkers of hepatotoxicity. Toxicology. 2008;245(3):194–205.PubMedCrossRef
42.
43.
Silva MRMA, Pacheco CMF, Madeira MFM, Saraiva AM, Freitas EA, Valverde TM, Gomes JHS, Pádua RM, Kitten GT, Alves SYF, et al. Effect of the extract and constituents from Hancornia speciosa fruits in osteoclasts. Planta Med. 2019;6(01):e7–e14.
44.
Chen X, Li X, Zhai X, Zhi X, Cao L, Qin L, Su J. Shikimic acid inhibits Osteoclastogenesis in vivo and in vitro by blocking RANK/TRAF6 association and suppressing NF-kappaB and MAPK signaling pathways. Cell Physiol Biochem. 2018;51(6):2858–71.PubMedCrossRef
45.
Wu YX, Wu TY, Xu BB, Xu XY, Chen HG, Li XY, Wang G. Protocatechuic acid inhibits osteoclast differentiation and stimulates apoptosis in mature osteoclasts. Biomed Pharmacother. 2016;82:399–405.PubMedCrossRef
46.
Kwak SC, Lee C, Kim JY, Oh HM, So HS, Lee MS, Rho MC, Oh J. Chlorogenic acid inhibits osteoclast differentiation and bone resorption by down-regulation of receptor activator of nuclear factor kappa-B ligand-induced nuclear factor of activated T cells c1 expression. Biol Pharm Bull. 2013;36(11):1779–86.PubMedCrossRef
47.
Ng AY, Tu C, Shen S, Xu D, Oursler MJ, Qu J, Yang S. Comparative characterization of osteoclasts derived from murine bone marrow macrophages and RAW 264.7 cells using quantitative proteomics. JBMR Plus. 2018;2(6):328–40.PubMedPubMedCentralCrossRef
48.
Adams GJ, Cook RB, Hutchinson JR, Zioupos P. Bone Apparent and Material Densities Examined by Cone Beam Computed Tomography and the Archimedes Technique: Comparison of the Two Methods and Their Results. Front Mech Eng. 2018:3(23).
Metadata
Title
Chaenomelis fructus inhibits osteoclast differentiation by suppressing NFATc1 expression and prevents ovariectomy-induced osteoporosis
Authors
Minsun Kim
Ho-Seok Kim
Jae-Hyun Kim
Eun-Young Kim
Bina Lee
Sung Yub Lee
Jae-Yun Jun
Min Beom Kim
Youngjoo Sohn
Hyuk-Sang Jung
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2020
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-020-2841-9

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