Skip to main content
Log in

Murine osteoblasts respond to LPS and IFN-γ similarly to macrophages

  • ORIGINAL ARTICLE
  • Published:
Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Osteoblasts are bone-forming mesenchymal cells, while macrophages are cells of hematopoietic origin responsible for innate immunity. Lipopolysaccharide (LPS) can induce tolerance in macrophages, whereas interferon (IFN)-γ can activate macrophages to produce cytokines, exert bactericidal effects, and present antigens. In this study, we examined such macrophagic phenotypes regulated by LPS and IFN-γ in murine osteoblasts. In both primary calvarial osteoblasts and osteoblastic MC3T3-E1 cells, LPS pretreatment resulted in reduced production of IL-6 in response to a subsequent LPS stimulation or to Salmonella infection, indicating the existence of LPS-induced tolerance in osteoblasts. Furthermore, IFN-γ treatment of MC3T3-E1 cells resulted in both enhanced IL-6 production in response to LPS and upregulation of major histocompatibility complex class II (MHC II). Following infection, Salmonella-containing vacuoles (SCVs) were formed in MC3T3-E1 cells, and IFN-γ pretreatment enhanced bactericidal effects on intracellular Salmonella. Taken together, these observations indicate that osteoblasts can exhibit a subset of phenotypes reminiscent of macrophages in the course of bacterial infection.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. DP Lew FA Waldvogel (2004) ArticleTitleOsteomyelitis Lancet 364 369–379 Occurrence Handle15276398 Occurrence Handle1:CAS:528:DC%2BD2cXmtVSktbc%3D Occurrence Handle10.1016/S0140-6736(04)16727-5

    Article  PubMed  CAS  Google Scholar 

  2. DP Lew FA Waldvogel (1997) ArticleTitleOsteomyelitis N Engl J Med 336 999–1007 Occurrence Handle9077380 Occurrence Handle1:STN:280:ByiB383jvVA%3D Occurrence Handle10.1056/NEJM199704033361406

    Article  PubMed  CAS  Google Scholar 

  3. AH al-SAlem HA Ahmed S Qaisaruddin A Al-Jam'a AM Elbashier I Al-Dabbous (1992) ArticleTitleOsteomyelitis and septic arthritis in sickle cell disease in the eastern province of Saudi Arabia Int Orthop 16 398–402 Occurrence Handle1473897 Occurrence Handle1:STN:280:ByyC3MvpsVA%3D Occurrence Handle10.1007/BF00189627

    Article  PubMed  CAS  Google Scholar 

  4. R Medzhitov (2001) ArticleTitleToll-like receptors and innate immunity Nat Rev Immunol 1 135–145 Occurrence Handle11905821 Occurrence Handle1:CAS:528:DC%2BD38XlvF2qu74%3D Occurrence Handle10.1038/35100529

    Article  PubMed  CAS  Google Scholar 

  5. MJ Wick HG Ljunggren (1999) ArticleTitleProcessing of bacterial antigens for peptide presentation on MHC class I molecules Immunol Rev 172 153–162 Occurrence Handle10631944 Occurrence Handle1:CAS:528:DC%2BD3cXkvVaksg%3D%3D Occurrence Handle10.1111/j.1600-065X.1999.tb01363.x

    Article  PubMed  CAS  Google Scholar 

  6. G Karsenty EF Wagner (2002) ArticleTitleReaching a genetic and molecular understanding of skeletal development Dev Cell 2 389–406 Occurrence Handle11970890 Occurrence Handle1:CAS:528:DC%2BD38Xjt1ersb4%3D Occurrence Handle10.1016/S1534-5807(02)00157-0

    Article  PubMed  CAS  Google Scholar 

  7. WS Simonet DL Lacey CR Dunstan M Kelley MS Chang R Luthy HQ Nguyen S Wooden L Bennett T Boone et al. (1997) ArticleTitleOsteoprotegerin: a novel secreted protein involved in the regulation of bone density Cell 89 309–319 Occurrence Handle9108485 Occurrence Handle1:CAS:528:DyaK2sXislCgtLc%3D Occurrence Handle10.1016/S0092-8674(00)80209-3

    Article  PubMed  CAS  Google Scholar 

  8. H Yasuda N Shima N Nakagawa SI Mochizuki K Yano N Fujise Y Sato M Goto K Yamaguchi M Kuriyama et al. (1998) ArticleTitleIdentity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro Endocrinology 139 1329–1337 Occurrence Handle9492069 Occurrence Handle10.1210/en.139.3.1329

    Article  PubMed  Google Scholar 

  9. S Kanzaki M Ito Y Takada K Ogawa K Matsuo (2006) ArticleTitleResorption of auditory ossicles and hearing loss in mice lacking osteoproegerin Bone (NY) 39 414–419 Occurrence Handle1:CAS:528:DC%2BD28Xls1ejtLY%3D

    CAS  Google Scholar 

  10. T Kikuchi T Matsuguchi N Tsuboi A Mitani S Tanaka M Matsuoka G Yamamoto T Hishikawa T Noguchi Y Yoshikai (2001) ArticleTitleGene expression of osteoclast differentiation factor is induced by lipopolysaccharide in mouse osteoblasts via Toll-like receptors J Immunol 166 3574–3579 Occurrence Handle11207318 Occurrence Handle1:CAS:528:DC%2BD3MXhs1Oisb4%3D

    PubMed  CAS  Google Scholar 

  11. NA Gasper CC Petty LW Schrum I Marriott KL Bost (2002) ArticleTitleBacterium-induced CXCL10 secretion by osteoblasts can be mediated in part through toll-like receptor 4 Infect Immun 70 4075–4082 Occurrence Handle12117914 Occurrence Handle1:CAS:528:DC%2BD38XlsFCmsLc%3D Occurrence Handle10.1128/IAI.70.8.4075-4082.2002

    Article  PubMed  CAS  Google Scholar 

  12. KL Bost WK Ramp NC Nicholson JL Bento I Marriott MC Hudson (1999) ArticleTitleStaphylococcus aureus infection of mouse or human osteoblasts induces high levels of interleukin-6 and interleukin-12 production J Infect Dis 180 1912–1920 Occurrence Handle10558948 Occurrence Handle1:CAS:528:DC%2BD3cXivVSrtw%3D%3D Occurrence Handle10.1086/315138

    Article  PubMed  CAS  Google Scholar 

  13. GS Firestein (2003) ArticleTitleEvolving concepts of rheumatoid arthritis Nature (Lond) 423 356–361 Occurrence Handle1:CAS:528:DC%2BD3sXjs1ynu7c%3D Occurrence Handle10.1038/nature01661

    Article  CAS  Google Scholar 

  14. H Takayanagi K Ogasawara S Hida T Chiba S Murata K Sato A Takaoka T Yokochi H Oda K Tanaka et al. (2000) ArticleTitleT-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-α Nature (Lond) 408 600–605 Occurrence Handle1:CAS:528:DC%2BD3cXovFajs7c%3D Occurrence Handle10.1038/35046102

    Article  CAS  Google Scholar 

  15. KL Bost JL Bento JK Ellington I Marriott MC Hudson (2000) ArticleTitleInduction of colony-stimulating factor expression following Staphylococcus or Salmonella interaction with mouse or human osteoblasts Infect Immun 68 5075–5083 Occurrence Handle10948128 Occurrence Handle1:CAS:528:DC%2BD3cXmtVeks70%3D Occurrence Handle10.1128/IAI.68.9.5075-5083.2000

    Article  PubMed  CAS  Google Scholar 

  16. T Nishiwaki T Yamaguchi C Zhao H Amano DH Kurt P Bornstein Y Toyama K Matsuo (2006) ArticleTitleReduced expression of thrombospondins and craniofacial dysmorphism in mice overexpressing Fra1 J Bone Miner Res 21 596–604 Occurrence Handle16598380 Occurrence Handle1:CAS:528:DC%2BD28Xkt1Kqs70%3D Occurrence Handle10.1359/jbmr.051216

    Article  PubMed  CAS  Google Scholar 

  17. A Nagy M Gertsenstein K Vintersten R Behringer (2003) Manipulating the mouse embryo: A laboratory manual, 3rd ed Cold Spring Harbor Laboratory Press, Cold Spring Harbor New York 371–373

    Google Scholar 

  18. PA Gulig R Curtiss SuffixIII (1987) ArticleTitlePlasmid-associated virulence of Salmonella typhimurium Infect Immun 55 2891–2901 Occurrence Handle3316027 Occurrence Handle1:CAS:528:DyaL1cXhvFWmtg%3D%3D

    PubMed  CAS  Google Scholar 

  19. K Suda N Udagawa N Sato M Takami K Itoh JT Woo N Takahashi K Nagai (2004) ArticleTitleSuppression of osteoprotegerin expression by prostaglandin E2 is crucially involved in lipopolysaccharide-induced osteoclast formation J Immunol 172 2504–2510 Occurrence Handle14764723 Occurrence Handle1:CAS:528:DC%2BD2cXpslWqsg%3D%3D

    PubMed  CAS  Google Scholar 

  20. FJ Hughes LD Buttery MV Hukkanen A O'Donnell J Maclouf JM Polak (1999) ArticleTitleCytokine-induced prostaglandin E2 synthesis and cyclooxygenase-2 activity are regulated both by a nitric oxide-dependent and -independent mechanism in rat osteoblasts in vitro J Biol Chem 274 1776–1782 Occurrence Handle9880560 Occurrence Handle1:CAS:528:DyaK1MXpsFOmsA%3D%3D Occurrence Handle10.1074/jbc.274.3.1776

    Article  PubMed  CAS  Google Scholar 

  21. K Kagaya K Watanabe Y Fukazawa (1989) ArticleTitleCapacity of recombinant gamma interferon to activate macrophages for Salmonella-killing activity Infect Immun 57 609–615 Occurrence Handle2492266 Occurrence Handle1:CAS:528:DyaL1MXhtlegsb4%3D

    PubMed  CAS  Google Scholar 

  22. F Garcia-del Portillo MB Zwick KY Leung BB Finlay (1993) ArticleTitleSalmonella induces the formation of filamentous structures containing lysosomal membrane glycoproteins in epithelial cells Proc Natl Acad Sci U S A 90 10544–10548 Occurrence Handle8248143 Occurrence Handle1:CAS:528:DyaK2cXltFCrsg%3D%3D Occurrence Handle10.1073/pnas.90.22.10544

    Article  PubMed  CAS  Google Scholar 

  23. S Sato F Nomura T Kawai O Takeuchi PF Muhlradt K Takeda S Akira (2000) ArticleTitleSynergy and cross-tolerance between toll-like receptor (TLR) 2- and TLR4-mediated signaling pathways J Immunol 165 7096–7101 Occurrence Handle11120839 Occurrence Handle1:CAS:528:DC%2BD3cXovFygs7s%3D

    PubMed  CAS  Google Scholar 

  24. K Kobayashi LD Hernandez JE Galán CA Janeway SuffixJr R Medzhitov RA Flavell (2002) ArticleTitleIRAK-M is a negative regulator of Toll-like receptor signaling Cell 110 191–202 Occurrence Handle12150927 Occurrence Handle1:CAS:528:DC%2BD38XlvV2htrw%3D Occurrence Handle10.1016/S0092-8674(02)00827-9

    Article  PubMed  CAS  Google Scholar 

  25. R Nakagawa T Naka H Tsutsui M Fujimoto A Kimura T Abe E Seki S Sato O Takeuchi K Takeda et al. (2002) ArticleTitleSOCS-1 participates in negative regulation of LPS responses Immunity 17 677–687 Occurrence Handle12433373 Occurrence Handle1:CAS:528:DC%2BD38XovF2ls7w%3D Occurrence Handle10.1016/S1074-7613(02)00449-1

    Article  PubMed  CAS  Google Scholar 

  26. I Kinjyo T Hanada K Inagaki-Ohara H Mori D Aki M Ohishi H Yoshida M Kubo A Yoshimura (2002) ArticleTitleSOCS1/JAB is a negative regulator of LPS-induced macrophage activation Immunity 17 583–591 Occurrence Handle12433365 Occurrence Handle1:CAS:528:DC%2BD38XovF2lsro%3D Occurrence Handle10.1016/S1074-7613(02)00446-6

    Article  PubMed  CAS  Google Scholar 

  27. LW Schrum KL Bost MC Hudson I Marriott (2003) ArticleTitleBacterial infection induces expression of functional MHC class II molecules in murine and human osteoblasts Bone (NY) 33 812–821 Occurrence Handle1:CAS:528:DC%2BD3sXovVemt74%3D

    CAS  Google Scholar 

  28. KT Stanley C Vandort C Motyl J Endres DA Fox (2006) ArticleTitleImmunocompetent properties of human osteoblasts: interactions with T lymphocytes J Bone Miner Res 21 29–36 Occurrence Handle16355271 Occurrence Handle1:CAS:528:DC%2BD28Xpt1Sntw%3D%3D Occurrence Handle10.1359/JBMR.051004

    Article  PubMed  CAS  Google Scholar 

  29. H Takayanagi S Kim K Matsuo H Suzuki T Suzuki K Sato T Yokichi H Oda K Nakamura N Ida et al. (2002) ArticleTitleRANKL maintains bone homeostasis through c-Fos-dependent induction of interferon-β Nature (Lond) 416 744–749 Occurrence Handle1:CAS:528:DC%2BD38XjtVKksLo%3D Occurrence Handle10.1038/416744a

    Article  CAS  Google Scholar 

  30. N Kurihara D Bertolini T Suda Y Akiyama GD Roodman (1990) ArticleTitleIL-6 stimulates osteoclast-like multinucleated cell formation in long term human marrow cultures by inducing IL-1 release J Immunol 144 4226–4230 Occurrence Handle2341718 Occurrence Handle1:CAS:528:DyaK3cXksFOisbY%3D

    PubMed  CAS  Google Scholar 

  31. X Zhang JE Aubin TH Kim U Payne B Chiu RD Inman (2004) ArticleTitleSynovial fibroblasts infected with Salmonella enterica serovar Typhimurium mediate osteoclast differentiation and activation Infect Immun 72 7183–7189 Occurrence Handle15557643 Occurrence Handle1:CAS:528:DC%2BD2cXhtVGls7vO Occurrence Handle10.1128/IAI.72.12.7183-7189.2004

    Article  PubMed  CAS  Google Scholar 

  32. M Takami N Kim J Rho Y Choi (2002) ArticleTitleStimulation by toll-like receptors inhibits osteoclast differentiation J Immunol 169 1516–1523 Occurrence Handle12133979 Occurrence Handle1:CAS:528:DC%2BD38XlslWht7c%3D

    PubMed  CAS  Google Scholar 

  33. V Asensi E Valle A Meana J Fierer A Celada V Alvarez J Paz E Coto JA Carton JA Maradona et al. (2004) ArticleTitleIn vivo interleukin-6 protects neutrophils from apoptosis in osteomyelitis Infect Immun 72 3823–3828 Occurrence Handle15213123 Occurrence Handle1:CAS:528:DC%2BD2cXlslWju70%3D Occurrence Handle10.1128/IAI.72.7.3823-3828.2004

    Article  PubMed  CAS  Google Scholar 

  34. PH Warnke IN Springer PA Russo J Wiltfang H Essig M Kosmahl E Sherry Y Acil (2006) ArticleTitleInnate immunity in human bone Bone (NY) 38 400–408 Occurrence Handle1:CAS:528:DC%2BD28XhslyrtLo%3D

    CAS  Google Scholar 

  35. SH Ralston D Todd M Helfrich N Benjamin PS Grabowski (1994) ArticleTitleHuman osteoblast-like cells produce nitric oxide and express inducible nitric oxide synthase Endocrinology 135 330–336 Occurrence Handle7516867 Occurrence Handle1:CAS:528:DyaK2cXksl2ntr8%3D Occurrence Handle10.1210/en.135.1.330

    Article  PubMed  CAS  Google Scholar 

  36. K Matsuo DL Galson C Zhao L Peng C Laplace KZ Wang MA Bachler H Amano H Aburatani H Ishikawa et al. (2004) ArticleTitleNuclear factor of activated T-cells (NFAT) rescues osteoclastogenesis in precursors lacking c-Fos J Biol Chem 279 26475–26480 Occurrence Handle15073183 Occurrence Handle1:CAS:528:DC%2BD2cXkvVWgtr4%3D Occurrence Handle10.1074/jbc.M313973200

    Article  PubMed  CAS  Google Scholar 

  37. N Ray M Kuwahara Y Takada K Maruyama T Kawaguchi H Tsubone H Ishikawa K Matsuo (2006) ArticleTitlec-Fos suppresses systemic systemic inflammatory response to endotoxin Int Immunol 18 671–677 Occurrence Handle16569682 Occurrence Handle1:CAS:528:DC%2BD28XktlSis7s%3D Occurrence Handle10.1093/intimm/dxl004

    Article  PubMed  CAS  Google Scholar 

  38. AE Grigoriadis K Schellander ZQ Wang EF Wagner (1993) ArticleTitleOsteoblasts are target cells for transformation in c-fos transgenic mice J Cell Biol 122 685–701 Occurrence Handle8335693 Occurrence Handle1:CAS:528:DyaK3sXltFCmu74%3D Occurrence Handle10.1083/jcb.122.3.685

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Koichi Matsuo.

About this article

Cite this article

Maruyama, K., Sano, Gi. & Matsuo, K. Murine osteoblasts respond to LPS and IFN-γ similarly to macrophages. J Bone Miner Metab 24, 454–460 (2006). https://doi.org/10.1007/s00774-006-0708-x

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00774-006-0708-x

Key words

Navigation