Download PDF
Planta Med 2018; 84(11): 759-767
DOI: 10.1055/s-0043-124594
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Amentoflavone Inhibits Osteoclastogenesis and Wear Debris-Induced Osteolysis via Suppressing NF-κB and MAPKs Signaling Pathways

Zhen Zhang
1   Dalian Medical University, Dalian, Liaoning, China
2   Department of Orthopedics, Subei Peopleʼs Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu, China
,
Shuai Zhao
4   Xiangya Second Hospital, Central South University, Changsha, Hunan, China
,
Xiaolei Li
2   Department of Orthopedics, Subei Peopleʼs Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu, China
4   Xiangya Second Hospital, Central South University, Changsha, Hunan, China
,
Xiaoqi Zhuo
3   Peking University Third Hospital, Peking University, Beijing, China
,
Wu Zhang
1   Dalian Medical University, Dalian, Liaoning, China
2   Department of Orthopedics, Subei Peopleʼs Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu, China
,
Qian Nie
2   Department of Orthopedics, Subei Peopleʼs Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu, China
,
Shuguang Wang
2   Department of Orthopedics, Subei Peopleʼs Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu, China
,
Lianqi Yan
1   Dalian Medical University, Dalian, Liaoning, China
2   Department of Orthopedics, Subei Peopleʼs Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu, China
4   Xiangya Second Hospital, Central South University, Changsha, Hunan, China
,
Yu Sun
2   Department of Orthopedics, Subei Peopleʼs Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu, China
› Author Affiliations
Further Information

Publication History

received 10 June 2017
revised 02 December 2017

accepted 05 December 2017

Publication Date:
04 January 2018 (online)

    Permissions and Reprints

Abstract

Wear debris-induced osteolysis is one of the major reasons for subsequent aseptic loosening after cementless hip arthroplasty. Increasing evidence suggests that receptor activator of nuclear factor kappa-B (NF-κB) ligand-mediated osteoclastogenesis and osteolysis are responsible for wear debris-induced aseptic loosening. In the present study, we explored the effect of amentoflavone (AMF) on inhibiting osteoclast generation and wear debris-induced osteolysis in vitro and in vivo. Twenty-four male C57BL/J6 mice were randomly divided into four groups: a sham group and groups with titanium wear debris treatment followed by intraperitoneal injection of various concentrations of AMF (0, 20, and 40 mg/kg/day). The micro computed tomography scanning and histological analysis were performed. Bone marrow-derived macrophages were cultured to investigate the effect of AMF on osteoclast generation and function. The results showed that AMF suppressed osteoclastogenesis, F-actin ring formation, and bone absorption without cytotoxicity. AMF prevented titanium wear debris-induced osteolysis in mice. AMF suppressed the relative proteins of NF-κB and mitogen-activated protein kinase (MAPKs) signaling pathways. Thus, the present study suggests that AMF derived from plants could inhibit osteoclastogenesis and titanium wear debris-induced osteolysis via suppressing NF-κB and MAPKs signaling pathways.

Key words

amentoflavone - osteoclastogenesis - osteolysis - RANKL - MAPKs - NF-κB
 

  • References

  • 1 Schnaser EA, Browne JA, Padgett DE, Figgie MP, DʼApuzzo MR. Perioperative complications in patients with inflammatory arthropathy undergoing total hip arthroplasty. J Arthroplasty 2016; 31: 2286-2290
    CrossrefPubMedGoogle Scholar
  • 2 Kurtz S, Ong K, Lau E, Mowat F, Halpern M. Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J Bone Joint Surg Am 2007; 89: 780-785
    CrossrefPubMedGoogle Scholar
  • 3 Studers P, Belajevs D, Jurkevics V, Likums P. Ten to fifteen-year clinical and radiographic follow-up with a third-generation cementless stem in a young patient population. Int Orthop 2016; 40: 465-471
    CrossrefPubMedGoogle Scholar
  • 4 Strauss AC, Rommelspacher Y, Nouri B, Bornemann R, Wimmer MD, Oldenburg J, Pennekamp PH, Schmolders J. Long-term outcome of total hip arthroplasty in patients with haemophilia. Haemophilia 2017; 23: 129-134
    CrossrefPubMedGoogle Scholar
  • 5 Singh JA, Sloan JA. Health-related quality of life in veterans with prevalent total knee arthroplasty and total hip arthroplasty. Rheumatology (Oxford) 2008; 47: 1826-1831
    CrossrefPubMedGoogle Scholar
  • 6 Ryan P, Saleh I, Stassen LF. Osteonecrosis of the jaw: a rare and devastating side effect of bisphosphonates. Postgrad Med J 2009; 85: 674-677
    CrossrefPubMedGoogle Scholar
  • 7 Fadda V, Maratea D, Trippoli S, Messori A. Gastrointestinal and renal side effects of bisphosphonates: differentiating between no proof of difference and proof of no difference. J Endocrinol Invest 2015; 38: 189-192
    CrossrefPubMedGoogle Scholar
  • 8 Goodman SB. Wear particles periprosthetic osteolysis and the immune system. Biomaterials 2007; 28: 5044-5048
    CrossrefPubMedGoogle Scholar
  • 9 Hundric-Haspl Z, Pecina M, Haspl M, Tomicic M, Jukic I. Plasma cytokines as markers of aseptic prosthesis loosening. Clin Orthop Relat Res 2006; 453: 299-304
    CrossrefPubMedGoogle Scholar
  • 10 Ross FP, Teitelbaum SL. Alphavbeta3 and macrophage colony-stimulating factor: partners in osteoclast biology. Immunol Rev 2005; 208: 88-105
    CrossrefPubMedGoogle Scholar
  • 11 Tanaka S, Takahashi N, Udagawa N, Tamura T, Akatsu T, Stanley ER, Kurokawa T, Suda T. Macrophage colony-stimulating factor is indispensable for both proliferation and differentiation of osteoclast progenitors. J Clin Invest 1993; 91: 257-263
    CrossrefPubMedGoogle Scholar
  • 12 Raimondo A, Lembo S, Di Caprio R, Donnarumma G, Monfrecola G, Balato N, Ayala F, Balato A. Psoriatic cutaneous inflammation promotes human monocyte differentiation into active osteoclasts, facilitating bone damage. Eur J Immunol 2017; 47: 1062-1074
    CrossrefPubMedGoogle Scholar
  • 13 OʼBrien W, Fissel BM, Maeda Y, Yan J, Ge X, Gravallese EM. Aliprantis AO, Charles JF. RANK-independent osteoclast formation and bone erosion in inflammatory arthritis. Arthritis Rheumatol 2016; 68: 2889-2900
    CrossrefPubMedGoogle Scholar
  • 14 Liu JZ, Ji ZJ, Chen SM. The OPG/RANKL/RANK system and bone resorptive disease. Sheng Wu Gong Cheng Xue Bao 2003; 19: 655-660
    PubMedGoogle Scholar
  • 15 Fu Y, Gu J, Wang Y, Yuan Y, Liu X, Bian J, Liu Z. Involvement of the mitogenactivated protein kinase signaling pathway in osteoprotegerininduced inhibition of osteoclast differentiation and maturation. Mol Med Rep 2015; 12: 6939-6945
    CrossrefPubMedGoogle Scholar
  • 16 Han BH, Lee YJ, Yoon JJ, Choi ES, Namgung S, Jin XJ, Jeong DH, Kang DG, Lee HS. Hwangryunhaedoktang exerts anti-inflammation on LPS-induced NO production by suppressing MAPK and NF-κB activation in RAW264.7 macrophages. J Integr Med 2017; 15: 326-336
    CrossrefPubMedGoogle Scholar
  • 17 Karki R, Park CH, Kim DW. Extract of buckwheat sprouts scavenges oxidation and inhibits pro-inflammatory mediators in lipopolysaccharide-stimulated macrophages (RAW264.7). J Integr Med 2013; 11: 246-252
    CrossrefPubMedGoogle Scholar
  • 18 Lee K, Chung YH, Ahn H, Kim H, Rho J, Jeong SD. Selective regulation of MAPK signaling mediates RANKL-dependent osteoclast differentiation. Int J Biol Sci 2016; 12: 235-245
    CrossrefPubMedGoogle Scholar
  • 19 Lin TH, Tamaki Y, Pajarinen J, Waters HA, Woo DK, Yao Z, Goodman SB. Chronic inflammation in biomaterial-induced periprosthetic osteolysis: NF-κB as a therapeutic target. Acta Biomater 2014; 10: 1-10
    CrossrefPubMedGoogle Scholar
  • 20 Hu X, Ping Z, Gan M, Tao Y, Wang L, Shi J, Wu X, Zhang W, Yang H, Xu Y, Wang Z, Geng D. Theaflavin-3,3′-digallate represses osteoclastogenesis and prevents wear debris-induced osteolysis via suppression of ERK pathway. Acta Biomater 2017; 48: 479-488
    CrossrefPubMedGoogle Scholar
  • 21 An J, Li Z, Dong Y, Ren J, Huo J. Amentoflavone protects against psoriasis-like skin lesion through suppression of NF-κB-mediated inflammation and keratinocyte proliferation. Mol Cell Biochem 2016; 413: 87-95
    CrossrefPubMedGoogle Scholar
  • 22 Zha X, Xu Z, Liu Y, Xu L, Huang H, Zhang J, Cui L, Zhou C, Xu D. Amentoflavone enhances osteogenesis of human mesenchymal stem cells through JNK and p38 MAPK pathways. J Nat Med 2016; 70: 634-644
    CrossrefPubMedGoogle Scholar
  • 23 Lee MK, Lim SW, Yang H, Sung SH, Lee HS, Park MJ, Kim YC. Osteoblast differentiation stimulating activity of biflavonoids from Cephalotaxus koreana . Bioorg Med Chem Lett 2006; 16: 2850-2854
    CrossrefPubMedGoogle Scholar
  • 24 Saltel F, Destaing O, Bard F, Eichert D, Jurdic P. Apatite-mediated actin dynamics in resorbing osteoclasts. Mol Biol Cell 2004; 15: 5231-5241
    CrossrefPubMedGoogle Scholar
  • 25 Lakkakorpi PT, Vaananen HK. Cytoskeletal changes in osteoclasts during the resorption cycle. Microsc Res Tech 1996; 33: 171-181
    CrossrefPubMedGoogle Scholar
  • 26 Marchisio PC, Cirillo D, Naldini L, Primavera MV, Teti A, Zambonin-Zallone A. Cell-substratum interaction of cultured avian osteoclasts is mediated by specific adhesion structures. J Cell Biol 1984; 99: 1696-1705
    CrossrefPubMedGoogle Scholar
  • 27 Akisaka T, Yoshida H, Inoue S, Shimizu K. Organization of cytoskeletal F-actin, G-actin, and gelsolin in the adhesion structures in cultured osteoclast. J Bone Miner Res 2001; 16: 1248-1255
    CrossrefPubMedGoogle Scholar
  • 28 Ren K, Purdue PE, Burton L, Quan LD, Fehringer EV, Thiele GM, Goldring SR, Wang D. Early detection and treatment of wear particle-induced inflammation and bone loss in a mouse calvarial osteolysis model using HPMA copolymer conjugates. Mol Pharm 2011; 8: 1043-1051
    CrossrefPubMedGoogle Scholar
  • 29 Guruvayoorappan C, Kuttan G. Effect of amentoflavone on the inhibition of pulmonary metastasis induced by B16F-10 melanoma cells in C57BL/6 mice. Integr Cancer Ther 2007; 6: 185-197
    CrossrefPubMedGoogle Scholar
  • 30 Guruvayoorappan C, Kuttan G. Inhibition of tumor specific angiogenesis by amentoflavone. Biochemistry (Mosc) 2008; 73: 209-218
    PubMedGoogle Scholar
  • 31 Nakamura H, Hirata A, Tsuji T, Yamamoto T. Role of osteoclast extracellular signal-regulated kinase (ERK) in cell survival and maintenance of cell polarity. J Bone Miner Res 2003; 18: 1198-1205
    CrossrefPubMedGoogle Scholar
  • 32 Vaira S, Alhawagri M, Anwisye I, Kitaura H, Faccio R, Novack DV. RelA/p65 promotes osteoclast differentiation by blocking a RANKL-induced apoptotic JNK pathway in mice. J Clin Invest 2008; 118: 2088-2097
    PubMedGoogle Scholar
  • 33 Xing L, Carlson L, Story B, Tai Z, Keng P, Siebenlist U, Boyce BF. Expression of either NF-κB p50 or p52 in osteoclast precursors is required for IL-1-induced bone resorption. J Bone Miner Res 2003; 8: 260-269
    PubMedGoogle Scholar
  • 34 Wu M, Wang Y, Deng L, Chen W, Li YP. TRAF family member-associated NF-κB activator (TANK) induced by RANKL negatively regulates osteoclasts survival and function. Int J Biol Sci 2012; 8: 1398-1407
    CrossrefPubMedGoogle Scholar
  • 35 Takatsuna H, Asagiri M, Kubota T, Oka K, Osada T, Sugiyama C, Saito H, Aoki K, Ohya K, Takayanagi H, Umezawa K. Inhibition of RANKL-induced osteoclastogenesis by (−)-DHMEQ, a novel NF-κB inhibitor, through downregulation of NFATc1. J Bone Miner Res 2005; 20: 653-662
    PubMedGoogle Scholar
  • 36 Asagiri M, Sato K, Usami T, Ochi S, Nishina H, Yoshida H, Morita I, Wagner EF, Mak TW, Serfling E, Takayanagi H. Autoamplification of NFATc1 expression determines its essential role in bone homeostasis. J Exp Med 2005; 202: 1261-1269
    CrossrefPubMedGoogle Scholar
  • 37 Gohda J, Akiyama T, Koga T, Takayanagi H, Tanaka S, Inoue J. RANK-mediated amplification of TRAF6 signaling leads to NFATc1 induction during osteoclastogenesis. EMBO J 2005; 24: 790-799
    CrossrefPubMedGoogle Scholar
  • 38 Matsuo K, Galson DJ, Zhao C, Peng L, Laplace C, Wang KZ, Bachler MA, Amano H, Aburatani H, Ishikawa H, Wagner EF. Nuclear factor of activated T-cells (NFAT) rescues osteoclastogenesis in precursors lacking c-Fos. J Biol Chem 2004; 279: 26475-26480
    CrossrefPubMedGoogle Scholar
  • 39 Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian YX, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 1998; 93: 165-176
    CrossrefPubMedGoogle Scholar
  • 40 Alfaqeeh S, Oralova V, Foxworthy M, Matalova E, Grigoriadis AE, Tucker AS. Root and eruption defects in c-Fos mice are driven by loss of osteoclasts. J Dent Res 2015; 94: 1724-1731
    CrossrefPubMedGoogle Scholar
  • 41 Baum R, Gravallese EM. Bone as a target organ in rheumatic disease: impact on osteoclasts and osteoblasts. Clin Rev Allergy Immunol 2016; 51: 1-15
    CrossrefPubMedGoogle Scholar
  • 42 Kitazawa S, Ross FP, McHugh K, Teitelbaum SL. Interleukin-4 induces expression of the integrin alpha v beta 3 via transactivation of the beta 3 gene. J Biol Chem 1995; 270: 4115-4120
    CrossrefPubMedGoogle Scholar
  • 43 von Knoch F, Wedemeyer C, Heckelei A, Saxler G, Hilken G, Brankamp J, Sterner T, Landgraeber S, Henschke F, Loer F, von Knoch M. Promotion of bone formation by simvastatin in polyethylene particle-induced osteolysis. Biomaterials 2005; 26: 5783-5789
    CrossrefPubMedGoogle Scholar
  • 44 Ragab AA, Van De Motter R, Lavish SA, Goldberg VM, Ninomiya JT, Carlin CR, Greenfield EM. Measurement and removal of adherent endotoxin from titanium particles and implant surfaces. J Orthop Res 1999; 17: 803-809
    CrossrefPubMedGoogle Scholar
  • 45 Yang H, Xu Y, Zhu M, Gu Y, Zhang W, Shao H, Wang Y, Ping Z, Hu X, Wang L, Geng D. Inhibition of titanium-particle-induced inflammatory osteolysis after local administration of dopamine and suppression of osteoclastogenesis via D2-like receptor signaling pathway. Biomaterials 2016; 80: 1-10
    CrossrefPubMedGoogle Scholar