Top

Published in:

01-10-2018 | Original Research

C-X-C Motif Chemokine 12 Enhances Lipopolysaccharide-Induced Osteoclastogenesis and Bone Resorption In Vivo

Authors: Kazuhiro Shima, Keisuke Kimura, Masahiko Ishida, Akiko Kishikawa, Saika Ogawa, Jiawei Qi, Wei-Ren Shen, Fumitoshi Ohori, Takahiro Noguchi, Aseel Marahleh, Hideki Kitaura

Published in: Calcified Tissue International | Issue 4/2018

Abstract

C-X-C motif chemokine 12 (CXCL12) belongs to the family of CXC chemokines. Lipopolysaccharide (LPS) induces inflammation-induced osteoclastogenesis and bone resorption, and in recent years, stimulatory effects of CXCL12 on bone resorption have also been reported. In the present study, we investigated the effects of CXCL12 on LPS-induced osteoclastogenesis and bone resorption. LPS was administered with or without CXCL12 onto mouse calvariae by daily subcutaneous injection. Numbers of osteoclasts and bone resorption were significantly elevated in mice co-administered LPS and CXCL12 compared with mice administered LPS alone. Moreover, receptor activator of NF-kB ligand (RANKL) and tumor necrosis factor-α (TNF-α) mRNA levels were higher in mice co-administered LPS and CXCL12 compared with mice administered LPS alone. These in vitro results confirmed a direct stimulatory effect of CXCL12 on RANKL- and TNF-α-induced osteoclastogenesis. Furthermore, TNF-α and RANKL mRNA levels were elevated in macrophages and osteoblasts, respectively, co-treated in vitro with CXCL12 and LPS, in comparison with cells treated with LPS alone. Our results suggest that CXCL12 enhances LPS-induced osteoclastogenesis and bone resorption in vivo through a combination of increasing LPS-induced TNF-α production by macrophages, increasing RANKL production by osteoblasts, and direct enhancement of osteoclastogenesis.

Crotti TN, Dharmapatni AA, Alias E, Haynes DR (2015) Osteoimmunology: major and costimulatory pathway expression associated with chronic inflammatory induced bone loss. J Immunol Res 2015:281287. https://doi.org/10.1155/2015/281287 CrossRefPubMedPubMedCentral

Teitelbaum SL (2007) Osteoclasts: what do they do and how do they do it? Am J Pathol 170(2):427–435. https://doi.org/10.2353/ajpath.2007.060834 CrossRefPubMedPubMedCentral

Azuma Y, Kaji K, Katogi R, Takeshita S, Kudo A (2000) Tumor necrosis factor-alpha induces differentiation of and bone resorption by osteoclasts. J Biol Chem 275(7):4858–4864CrossRefPubMed

Kobayashi K, Takahashi N, Jimi E, Udagawa N, Takami M, Kotake S, Nakagawa N, Kinosaki M, Yamaguchi K, Shima N, Yasuda H, Morinaga T, Higashio K, Martin TJ, Suda T (2000) Tumor necrosis factor alpha stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL-RANK interaction. J Exp Med 191(2):275–286CrossRefPubMedPubMedCentral

Fuller K, Murphy C, Kirstein B, Fox SW, Chambers TJ (2002) TNFalpha potently activates osteoclasts, through a direct action independent of and strongly synergistic with RANKL. Endocrinology 143(3):1108–1118. https://doi.org/10.1210/endo.143.3.8701 CrossRefPubMed

Kitaura H, Sands MS, Aya K, Zhou P, Hirayama T, Uthgenannt B, Wei S, Takeshita S, Novack DV, Silva MJ, Abu-Amer Y, Ross FP, Teitelbaum SL (2004) Marrow stromal cells and osteoclast precursors differentially contribute to TNF-alpha-induced osteoclastogenesis in vivo. J Immunol 173(8):4838–4846CrossRefPubMed

Kitaura H, Zhou P, Kim HJ, Novack DV, Ross FP, Teitelbaum SL (2005) M-CSF mediates TNF-induced inflammatory osteolysis. J Clin Invest 115(12):3418–3427. https://doi.org/10.1172/JCI26132 CrossRefPubMedPubMedCentral

Li P, Schwarz EM, O’Keefe RJ, Ma L, Boyce BF, Xing L (2004) RANK signaling is not required for TNFalpha-mediated increase in CD11(hi) osteoclast precursors but is essential for mature osteoclast formation in TNFalpha-mediated inflammatory arthritis. J Bone Miner Res 19(2):207–213. https://doi.org/10.1359/JBMR.0301233 CrossRefPubMed

Abu-Amer Y, Ross FP, Edwards J, Teitelbaum SL (1997) Lipopolysaccharide-stimulated osteoclastogenesis is mediated by tumor necrosis factor via its P55 receptor. J Clin Invest 100(6):1557–1565. https://doi.org/10.1172/JCI119679 CrossRefPubMedPubMedCentral

10.

Dumitrescu AL, Abd-El-Aleem S, Morales-Aza B, Donaldson LF (2004) A model of periodontitis in the rat: effect of lipopolysaccharide on bone resorption, osteoclast activity, and local peptidergic innervation. J Clin Periodontol 31(8):596–603. https://doi.org/10.1111/j.1600-051X.2004.00528.x CrossRefPubMed

11.

Bostanci N, Allaker RP, Belibasakis GN, Rangarajan M, Curtis MA, Hughes FJ, McKay IJ (2007) Porphyromonas gingivalis antagonises Campylobacter rectus induced cytokine production by human monocytes. Cytokine 39(2):147–156. https://doi.org/10.1016/j.cyto.2007.07.002 CrossRefPubMed

12.

Kitaura H, Kimura K, Ishida M, Kohara H, Yoshimatsu M, Takano-Yamamoto T (2013) Immunological reaction in TNF-alpha-mediated osteoclast formation and bone resorption in vitro and in vivo. Clin Dev Immunol 2013:181849. https://doi.org/10.1155/2013/181849 CrossRefPubMedPubMedCentral

13.

Zou W, Bar-Shavit Z (2002) Dual modulation of osteoclast differentiation by lipopolysaccharide. J Bone Miner Res 17(7):1211–1218. https://doi.org/10.1359/jbmr.2002.17.7.1211 CrossRefPubMed

14.

Kikuchi T, Matsuguchi T, Tsuboi N, Mitani A, Tanaka S, Matsuoka M, Yamamoto G, Hishikawa T, Noguchi T, Yoshikai Y (2001) Gene expression of osteoclast differentiation factor is induced by lipopolysaccharide in mouse osteoblasts via Toll-like receptors. J Immunol 166(5):3574–3579CrossRefPubMed

15.

Lee J, Park C, Kim HJ, Lee YD, Lee ZH, Song YW, Kim HH (2017) Stimulation of osteoclast migration and bone resorption by C-C chemokine ligands 19 and 21. Exp Mol Med 49(7):e358. https://doi.org/10.1038/emm.2017.100 CrossRefPubMedPubMedCentral

16.

Yu X, Huang Y, Collin-Osdoby P, Osdoby P (2004) CCR1 chemokines promote the chemotactic recruitment, RANKL development, and motility of osteoclasts and are induced by inflammatory cytokines in osteoblasts. J Bone Miner Res 19(12):2065–2077. https://doi.org/10.1359/JBMR.040910 CrossRefPubMed

17.

Votta BJ, White JR, Dodds RA, James IE, Connor JR, Lee-Rykaczewski E, Eichman CF, Kumar S, Lark MW, Gowen M (2000) CKbeta-8 [CCL23], a novel CC chemokine, is chemotactic for human osteoclast precursors and is expressed in bone tissues. J Cell Physiol 183 (2):196–207CrossRefPubMed

18.

Pawig L, Klasen C, Weber C, Bernhagen J, Noels H (2015) Diversity and inter-connections in the CXCR4 Chemokine receptor/ligand family: molecular perspectives. Front Immunol 6:429. https://doi.org/10.3389/fimmu.2015.00429 CrossRefPubMedPubMedCentral

19.

Schrader AJ, Lechner O, Templin M, Dittmar KE, Machtens S, Mengel M, Probst-Kepper M, Franzke A, Wollensak T, Gatzlaff P, Atzpodien J, Buer J, Lauber J (2002) CXCR4/CXCL12 expression and signalling in kidney cancer. Br J Cancer 86(8):1250–1256. https://doi.org/10.1038/sj.bjc.6600221 CrossRefPubMedPubMedCentral

20.

Ma Q, Jones D, Borghesani PR, Segal RA, Nagasawa T, Kishimoto T, Bronson RT, Springer TA (1998) Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice. Proc Natl Acad Sci USA 95(16):9448–9453CrossRefPubMed

21.

Bleul CC, Fuhlbrigge RC, Casasnovas JM, Aiuti A, Springer TA (1996) A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1). J Exp Med 184(3):1101–1109CrossRefPubMed

22.

Kincade PW (2010) Plasticity of supporting cells in a stem cell factory. Immunity 33(3):291–293. https://doi.org/10.1016/j.immuni.2010.09.003 CrossRefPubMed

23.

Pramanik R, Sheng X, Ichihara B, Heisterkamp N, Mittelman SD (2013) Adipose tissue attracts and protects acute lymphoblastic leukemia cells from chemotherapy. Leuk Res 37(5):503–509. https://doi.org/10.1016/j.leukres.2012.12.013 CrossRefPubMedPubMedCentral

24.

Okada K, Kawao N, Yano M, Tamura Y, Kurashimo S, Okumoto K, Kojima K, Kaji H (2016) Stromal cell-derived factor-1 mediates changes of bone marrow stem cells during the bone repair process. Am J Physiol Endocrinol Metab 310(1):E15–E23. https://doi.org/10.1152/ajpendo.00253.2015 CrossRef

25.

Teixido J, Martinez-Moreno M, Diaz-Martinez M, Sevilla-Movilla S (2018) The good and bad faces of the CXCR4 chemokine receptor. Int J Biochem Cell Biol 95:121–131. https://doi.org/10.1016/j.biocel.2017.12.018 CrossRefPubMed

26.

Luo T, Liu H, Feng W, Liu D, Du J, Sun J, Wang W, Han X, Guo J, Amizuka N, Li X, Li M (2017) Adipocytes enhance expression of osteoclast adhesion-related molecules through the CXCL12/CXCR4 signalling pathway. Cell Prolif. https://doi.org/10.1111/cpr.12317 CrossRefPubMed

27.

Dong Y, Liu H, Zhang X, Xu F, Qin L, Cheng P, Huang H, Guo F, Yang Q, Chen A (2016) Inhibition of SDF-1alpha/CXCR4 signalling in subchondral bone attenuates post-traumatic osteoarthritis. Int J Mol Sci. https://doi.org/10.3390/ijms17060943 CrossRefPubMedPubMedCentral

28.

McHugh KP, Hodivala-Dilke K, Zheng MH, Namba N, Lam J, Novack D, Feng X, Ross FP, Hynes RO, Teitelbaum SL (2000) Mice lacking beta3 integrins are osteosclerotic because of dysfunctional osteoclasts. J Clin Invest 105(4):433–440. https://doi.org/10.1172/JCI8905 CrossRefPubMedPubMedCentral

29.

Takeshita S, Kaji K, Kudo A (2000) Identification and characterization of the new osteoclast progenitor with macrophage phenotypes being able to differentiate into mature osteoclasts. J Bone Miner Res 15(8):1477–1488. https://doi.org/10.1359/jbmr.2000.15.8.1477 CrossRefPubMed

30.

Kimura K, Kitaura H, Fujii T, Hakami ZW, Takano-Yamamoto T (2012) Anti-c-Fms antibody inhibits lipopolysaccharide-induced osteoclastogenesis in vivo. FEMS Immunol Med Microbiol 64(2):219–227. https://doi.org/10.1111/j.1574-695X.2011.00888.x CrossRefPubMed

31.

Saeed J, Kitaura H, Kimura K, Ishida M, Sugisawa H, Ochi Y, Kishikawa A, Takano-Yamamoto T (2016) IL-37 inhibits lipopolysaccharide-induced osteoclast formation and bone resorption in vivo. Immunol Lett 175:8–15. https://doi.org/10.1016/j.imlet.2016.04.004 CrossRefPubMed

32.

Ishida M, Kitaura H, Kimura K, Sugisawa H, Aonuma T, Takada H, Takano-Yamamoto T (2015) Muramyl dipeptide enhances lipopolysaccharide-induced osteoclast formation and bone resorption through increased RANKL expression in stromal cells. J Immunol Res 2015:132765. https://doi.org/10.1155/2015/132765 CrossRefPubMedPubMedCentral

33.

Bakker AD, Klein-Nulend J (2012) Osteoblast isolation from murine calvaria and long bones. Methods Mol Biol 816:19–29. https://doi.org/10.1007/978-1-61779-415-5_2 CrossRefPubMed

34.

Kanbe K, Takagishi K, Chen Q (2002) Stimulation of matrix metalloprotease 3 release from human chondrocytes by the interaction of stromal cell-derived factor 1 and CXC chemokine receptor 4. Arthritis Rheum 46(1):130–137CrossRefPubMed

35.

Nanki T, Hayashida K, El-Gabalawy HS, Suson S, Shi K, Girschick HJ, Yavuz S, Lipsky PE (2000) Stromal cell-derived factor-1-CXC chemokine receptor 4 interactions play a central role in CD4 + T cell accumulation in rheumatoid arthritis synovium. J Immunol 165(11):6590–6598CrossRefPubMed

36.

Pablos JL, Santiago B, Galindo M, Torres C, Brehmer MT, Blanco FJ, Garcia-Lazaro FJ (2003) Synoviocyte-derived CXCL12 is displayed on endothelium and induces angiogenesis in rheumatoid arthritis. J Immunol 170(4):2147–2152CrossRefPubMed

37.

De Klerck B, Geboes L, Hatse S, Kelchtermans H, Meyvis Y, Vermeire K, Bridger G, Billiau A, Schols D, Matthys P (2005) Pro-inflammatory properties of stromal cell-derived factor-1 (CXCL12) in collagen-induced arthritis. Arthritis Res Ther 7(6):R1208–R1220. https://doi.org/10.1186/ar1806 CrossRef

38.

Yang L, Wang M, Guo YY, Sun T, Li YJ, Yang Q, Zhang K, Liu SB, Zhao MG, Wu YM (2016) Systemic inflammation induces anxiety disorder through CXCL12/CXCR4 pathway. Brain Behav Immun 56:352–362. https://doi.org/10.1016/j.bbi.2016.03.001 CrossRefPubMed

39.

Konrad FM, Meichssner N, Bury A, Ngamsri KC, Reutershan J (2017) Inhibition of SDF-1 receptors CXCR4 and CXCR7 attenuates acute pulmonary inflammation via the adenosine A2B-receptor on blood cells. Cell Death Dis 8(5):e2832. https://doi.org/10.1038/cddis.2016.482 CrossRefPubMedPubMedCentral

40.

Xing Q, de Vos P, Faas MM, Ye Q, Ren Y (2011) LPS promotes pre-osteoclast activity by up-regulating CXCR4 via TLR-4. J Dent Res 90(2):157–162. https://doi.org/10.1177/0022034510379019 CrossRefPubMed

41.

Yu L, Yu L, Pham Q, Wang TTY (2018) Transcriptional and translational-uncoupling in regulation of the CXCL12 and its receptors CXCR4, 7 in THP-1 monocytes and macrophages. Immun Inflamm Dis 6(1):106–116. https://doi.org/10.1002/iid3.199 CrossRefPubMed

42.

Souza JAC, Nogueira AVB, Souza PPC, Oliveira G, Medeiros MC, Garlet GP, Cirelli JA, Rossa CJ (2017) Suppressor of cytokine signaling 1 expression during LPS-induced inflammation and bone loss in rats. Braz Oral Res 31:e75PubMed

43.

Kong L, Ma R, Yang X, Zhu Z, Guo H, He B, Wang B, Hao D (2017) Psoralidin suppresses osteoclastogenesis in BMMs and attenuates LPS-mediated osteolysis by inhibiting inflammatory cytokines. Int Immunopharmacol 51:31–39. https://doi.org/10.1016/j.intimp.2017.07.003 CrossRefPubMed

44.

Leite FR, de Aquino SG, Guimaraes MR, Cirelli JA, Zamboni DS, Silva JS, Junior CR (2015) Relevance of the myeloid differentiation factor 88 (MyD88) on RANKL, OPG, and nod expressions induced by TLR and IL-1R signaling in bone marrow stromal cells. Inflammation 38(1):1–8. https://doi.org/10.1007/s10753-014-0001-4 CrossRefPubMed

45.

Wada N, Maeda H, Yoshimine Y, Akamine A (2004) Lipopolysaccharide stimulates expression of osteoprotegerin and receptor activator of NF-kappa B ligand in periodontal ligament fibroblasts through the induction of interleukin-1 beta and tumor necrosis factor-alpha. Bone 35(3):629–635. https://doi.org/10.1016/j.bone.2004.04.023 CrossRefPubMed

Title: C-X-C Motif Chemokine 12 Enhances Lipopolysaccharide-Induced Osteoclastogenesis and Bone Resorption In Vivo
Authors: Kazuhiro Shima
Keisuke Kimura
Masahiko Ishida
Akiko Kishikawa
Saika Ogawa
Jiawei Qi
Wei-Ren Shen
Fumitoshi Ohori
Takahiro Noguchi
Aseel Marahleh
Hideki Kitaura
Publication date: 01-10-2018
Publisher: Springer US
Published in: Calcified Tissue International / Issue 4/2018
Print ISSN: 0171-967X
Electronic ISSN: 1432-0827
DOI: https://doi.org/10.1007/s00223-018-0435-z

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2018

The Effect of β-Aminopropionitrile on Skeletal Micromorphology and Osteogenesis

Effects of Teriparatide in Patients with Osteoporosis in Clinical Practice: 42-Month Results During and After Discontinuation of Treatment from the European Extended Forsteo® Observational Study (ExFOS)

lncRNA HOTAIR Inhibits Mineralization in Osteoblastic Osteosarcoma Cells by Epigenetically Repressing ALPL

Ficus deltoidea Prevented Bone Loss in Preclinical Osteoporosis/Osteoarthritis Model by Suppressing Inflammation

Periprosthetic Bone Mineral Density Around Uncemented Titanium Stems in the Second and Third Decade After Total Hip Arthroplasty: A DXA Study After 12, 17 and 21 Years

A Challenging Case of Tumor-Induced Osteomalacia: Pathophysiological and Clinical Implications

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials