Skip to main content

Advertisement

Log in

Effect of retinoic acid on the function of lipopolysaccharide-stimulated bone marrow stromal cells grown on titanium surfaces

  • Original Research Paper
  • Published:
Inflammation Research Aims and scope Submit manuscript

Abstract

Objective and design

This study aimed to evaluate the effect of all-trans retinoic acid (atRA) on suppressing the inflammatory response and promoting the osteoblastic differentiation of bone marrow stromal cells (BMSCs) on titanium in a lipopolysaccharide (LPS)-induced microenvironment.

Methods

BMSCs were divided into four groups and treated with LPS (1 μg/mL), atRA (1 nmol/L), LPS + atRA, or left untreated. Cells were then cultured on titanium surfaces and cell function compared. BMSC proliferation and osteoblastic differentiation were assessed using the MTT assay, alkaline phosphatase (ALP) activity, alizarin red staining, and quantitative real-time polymerase chain reaction (RT-PCR). Expression levels of inflammatory factors were measured by quantitative RT-PCR and enzyme-linked immunosorbent assay.

Results

Increased mineralized nodule formation, ALP activity, osteocalcin, and osteopontin expression levels were detected in LPS + atRA-treated BMSCs after osteogenic induction, when compared with LPS-treated cells. In addition, the high levels of tumor necrosis factor-α, interleukin-1β, and receptor activator of nuclear factor-κ B ligand (RANKL) expression induced by LPS were inhibited after treatment with atRA.

Conclusions

Our results showed the effects of atRA on suppressing inflammatory responses and promoting osteoblastic differentiation of BMSCs on titanium in an LPS-induced microenvironment. This indicates the potential therapeutic value of atRA for treating peri-implants inflammatory disease.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Esposito M, Hirsch JM, Lekholm U, Thomsen P. Biological factors contributing to failures of osseointegrated oral implants. (I). Success criteria and epidemiology. Eur J Oral Sci. 1998;106:527–51.

    Article  CAS  PubMed  Google Scholar 

  2. Koyanagi T, Sakamoto M, Takeuchi Y, Maruyama N, Ohkuma M, Izumi Y. Comprehensive microbiological findings in peri-implantitis and periodontitis. J Clin Periodontol. 2013;40:218–26.

    Article  PubMed  Google Scholar 

  3. Lamont RJ, Jenkinson HF. Life below the gum line: pathogenic mechanisms of Porphyromonas gingivalis. Microbiol Mol Biol Rev. 1998;62:1244–63.

    CAS  PubMed Central  PubMed  Google Scholar 

  4. Zhu C, Yang J, Sun J, Shi J, Gou J, Li A. Induction of immune response and prevention of alveolar bone loss with recombinant Porphyromonas gingivalis peptidylarginine deiminase. Arch Oral Biol. 2013;58:1777–83.

    Article  CAS  PubMed  Google Scholar 

  5. Kato H, Taguchi Y, Tominaga K, Umeda M, Tanaka A. Porphyromonas gingivalis LPS inhibits osteoblastic differentiation and promotes pro-inflammatory cytokine production in human periodontal ligament stem cells. Arch Oral Biol. 2014;59:167–75.

    Article  CAS  PubMed  Google Scholar 

  6. Bandow K, Maeda A, Kakimoto K, Kusuyama J, Shamoto M, Ohnishi T, et al. Molecular mechanisms of the inhibitory effect of lipopolysaccharide (LPS) on osteoblast differentiation. Biochem Biophys Res Commun. 2010;402:755–61.

    Article  CAS  PubMed  Google Scholar 

  7. Xing Q, Ye Q, Fan M, Zhou Y, Xu Q, Sandham A. Porphyromonas gingivalis lipopolysaccharide inhibits the osteoblastic differentiation of preosteoblasts by activating Notch1 signaling. J Cell Physiol. 2010;225:106–14.

    Article  CAS  PubMed  Google Scholar 

  8. Herath TD, Wang Y, Seneviratne CJ, Lu Q, Darveau RP, Wang CY, et al. Porphyromonas gingivalis lipopolysaccharide lipid A heterogeneity differentially modulates the expression of IL-6 and IL-8 in human gingival fibroblasts. J Clin Periodontol. 2011;38:694–701.

    Article  CAS  PubMed  Google Scholar 

  9. Nouneh RA, Wataha JC, Hanes PJ, Lockwood PE. Effect of lipopolysaccharide contamination on the attachment of osteoblast-like cells to titanium and titanium alloy in vitro. J Oral Implantol. 2001;27:174–9.

    Article  CAS  PubMed  Google Scholar 

  10. Walters SM, Dubey VS, Jeffrey NR, Dixon DR. Antibiotic-induced Porphyromonas gingivalis LPS release and inhibition of LPS-stimulated cytokines by antimicrobial peptides. Peptides. 2010;31:1649–53.

    Article  CAS  PubMed  Google Scholar 

  11. Ragab AA, Van De Motter R, Lavish SA, Goldberg VM, Ninomiya JT, Carlin CR, et al. Measurement and removal of adherent endotoxin from titanium particles and implant surfaces. J Orthop Res. 1999;17:803–9.

    Article  CAS  PubMed  Google Scholar 

  12. Bonsignore LA, Anderson JR, Lee Z, Goldberg VM, Greenfield EM. Adherent lipopolysaccharide inhibits the osseointegration of orthopedic implants by impairing osteoblast differentiation. Bone. 2013;52:93–101.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Yamano E, Miyauchi M, Furusyo H, Kawazoe A, Ishikado A, Makino T, et al. Inhibitory effects of orally administrated liposomal bovine lactoferrin on the LPS-induced osteoclastogenesis. Lab Invest. 2010;90:1236–46.

    Article  CAS  PubMed  Google Scholar 

  14. Semba RD. Vitamin A as “anti-infective” therapy, 1920–1940. J Nutr. 1999;129:783–91.

    CAS  PubMed  Google Scholar 

  15. Gu B, Miao J, Fa Y, Lu J, Zou S. Retinoic acid attenuates lipopolysaccharide-induced inflammatory responses by suppressing TLR4/NF-kappaB expression in rat mammary tissue. Int Immunopharmacol. 2010;10:799–805.

    Article  CAS  PubMed  Google Scholar 

  16. Wang X, Allen C, Ballow M. Retinoic acid enhances the production of IL-10 while reducing the synthesis of IL-12 and TNF-alpha from LPS-stimulated monocytes/macrophages. J Clin Immunol. 2007;27:193–200.

    Article  PubMed  Google Scholar 

  17. Weng Y, Wang M, Liu W, Hu X, Chai G, Yan Q, et al. Repair of experimental alveolar bone defects by tissue-engineered bone. Tissue Eng. 2006;12:1503–13.

    Article  CAS  PubMed  Google Scholar 

  18. Chen KY, Chung CM, Chen YS, Bau DT, Yao CH. Rat bone marrow stromal cells-seeded porous gelatin/tricalcium phosphate/oligomeric proanthocyanidins composite scaffold for bone repair. J Tissue Eng Regen Med. 2013;7:708–19.

    Article  CAS  PubMed  Google Scholar 

  19. Boeloni JN, Ocarino NM, Goes AM, Serakides R. Comparative study of osteogenic differentiation potential of mesenchymal stem cells derived from bone marrow and adipose tissue of osteoporotic female rats. Connect Tissue Res. 2013;55:103–14.

    Article  Google Scholar 

  20. Li X, Zhang Y, Qi G. Evaluation of isolation methods and culture conditions for rat bone marrow mesenchymal stem cells. Cytotechnology. 2013;65:323–34.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Amoroso PF, Adams RJ, Waters MG, Williams DW. Titanium surface modification and its effect on the adherence of Porphyromonas gingivalis: an in vitro study. Clin Oral Implants Res. 2006;17:633–7.

    Article  PubMed  Google Scholar 

  22. Colombo JS, Carley A, Fleming GJ, Crean SJ, Sloan AJ, Waddington RJ. Osteogenic potential of bone marrow stromal cells on smooth, roughened, and tricalcium phosphate-modified titanium alloy surfaces. Int J Oral Maxillofac Implants. 2012;27:1029–42.

    PubMed  Google Scholar 

  23. Li Y, Li J, Zhu S, Luo E, Feng G, Chen Q, et al. Effects of strontium on proliferation and differentiation of rat bone marrow mesenchymal stem cells. Biochem Biophys Res Commun. 2012;418:725–30.

    Article  CAS  PubMed  Google Scholar 

  24. Maggini J, Mirkin G, Bognanni I, Holmberg J, Piazzon IM, Nepomnaschy I, et al. Mouse bone marrow-derived mesenchymal stromal cells turn activated macrophages into a regulatory-like profile. PLoS One. 2010;5:e9252.

    Article  PubMed Central  PubMed  Google Scholar 

  25. Ocarino NM, Boeloni JN, Goes AM, Silva JF, Marubayashi U, Serakides R. Osteogenic differentiation of mesenchymal stem cells from osteopenic rats subjected to physical activity with and without nitric oxide synthase inhibition. Nitric Oxide. 2008;19:320–5.

    Article  CAS  PubMed  Google Scholar 

  26. Tang Y, Sun F, Li X, Zhou Y, Yin S, Zhou X. Porphyromonas endodontalis lipopolysaccharides induce RANKL by mouse osteoblast in a way different from that of Escherichia coli lipopolysaccharide. J Endod. 2011;37:1653–8.

    Article  PubMed  Google Scholar 

  27. Lee SK, Chung JH, Choi SC, Auh QS, Lee YM, Lee SI, et al. Sodium hydrogen sulfide inhibits nicotine and lipopolysaccharide-induced osteoclastic differentiation and reversed osteoblastic differentiation in human periodontal ligament cells. J Cell Biochem. 2013;114:1183–93.

    Article  CAS  PubMed  Google Scholar 

  28. Weinreb M, Shinar D, Rodan GA. Different pattern of alkaline phosphatase, osteopontin, and osteocalcin expression in developing rat bone visualized by in situ hybridization. J Bone Miner Res. 1990;5:831–42.

    Article  CAS  PubMed  Google Scholar 

  29. Hisada K, Hata K, Ichida F, Matsubara T, Orimo H, Nakano T, et al. Retinoic acid regulates commitment of undifferentiated mesenchymal stem cells into osteoblasts and adipocytes. J Bone Miner Metab. 2013;31:53–63.

    Article  CAS  PubMed  Google Scholar 

  30. Hu L, Lind T, Sundqvist A, Jacobson A, Melhus H. Retinoic acid increases proliferation of human osteoclast progenitors and inhibits RANKL-stimulated osteoclast differentiation by suppressing RANK. PLoS One. 2010;5:e13305.

    Article  PubMed Central  PubMed  Google Scholar 

  31. Abbas S, Zhang YH, Clohisy JC, Abu-Amer Y. Tumor necrosis factor-alpha inhibits pre-osteoblast differentiation through its type-1 receptor. Cytokine. 2003;22:33–41.

    Article  CAS  PubMed  Google Scholar 

  32. Lacey DC, Simmons PJ, Graves SE, Hamilton JA. Proinflammatory cytokines inhibit osteogenic differentiation from stem cells: implications for bone repair during inflammation. Osteoarthritis Cartilage. 2009;17:735–42.

    Article  CAS  PubMed  Google Scholar 

  33. Zhao G, Schwartz Z, Wieland M, Rupp F, Geis-Gerstorfer J, Cochran DL, et al. High surface energy enhances cell response to titanium substrate microstructure. J Biomed Mater Res A. 2005;74:49–58.

    Article  CAS  PubMed  Google Scholar 

  34. Nebe JG, Luethen F, Lange R, Beck U. Interface interactions of osteoblasts with structured titanium and the correlation between physicochemical characteristics and cell biological parameters. Macromol Biosci. 2007;7:567–78.

    Article  CAS  PubMed  Google Scholar 

  35. Wall I, Donos N, Carlqvist K, Jones F, Brett P. Modified titanium surfaces promote accelerated osteogenic differentiation of mesenchymal stromal cells in vitro. Bone. 2009;45:17–26.

    Article  CAS  PubMed  Google Scholar 

  36. Martire-Greco D, Landoni VI, Chiarella P, Rodriguez-Rodrigues N, Schierloh P, Rearte B, et al. all-trans-Retinoic acid improves immunocompetence in a murine model of lipopolysaccharide-induced immunosuppression. Clin Sci (Lond). 2014;126:355–65.

    Article  CAS  Google Scholar 

  37. Lind T, Sundqvist A, Hu L, Pejler G, Andersson G, Jacobson A, et al. Vitamin a is a negative regulator of osteoblast mineralization. PLoS One. 2013;8:e82388.

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the National Nature Science Foundation of China (No. 81170992). The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bin Shi.

Additional information

Responsible Editor: John Di Battista.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yan, Q., Li, Y., Cheng, N. et al. Effect of retinoic acid on the function of lipopolysaccharide-stimulated bone marrow stromal cells grown on titanium surfaces. Inflamm. Res. 64, 63–70 (2015). https://doi.org/10.1007/s00011-014-0784-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-014-0784-7

Keywords

Navigation