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01-06-2016 | Original Article

Short-term heat pre-treatment modulates the release of HMGB1 and pro-inflammatory cytokines in hPDL cells following mechanical loading and affects monocyte behavior

Authors: Michael Wolf, Stefan Lossdörfer, Piero Römer, Christian Kirschneck, Katharina Küpper, James Deschner, Andreas Jäger

Published in: Clinical Oral Investigations | Issue 5/2016

Abstract

Objective

Heat shock proteins (HSP) act as cell-protective molecules that are upregulated upon thermal insult, hypoxia, and ischemia. Such ischemic conditions can be found during tissue remodeling associated with orthodontic tooth movement or trauma when compression forces lead to cell necrosis and subsequent clearance of cellular debris by immune competent cells. Host immune overreaction can result in undesired side effects such as tooth root resorption. Here, we analyzed whether heat pre-treatment would affect the initially catabolic host immune response induced by mechanical loading of human periodontal ligament (hPDL) cells, which represent major constituents of the tooth supporting apparatus involved in the regulation of periodontal remodeling.

Materials and methods

Fifth passage hPDL cells were exposed to an elevated temperature of 43° for 1 h prior to mechanical loading. Cell morphology, high mobility group box protein 1 (HMGB1), interleukin (IL)-6, and IL-8 expression were analyzed microscopically and by ELISA. The physiological relevance for monocyte behavior was tested in monocyte adhesion and osteoclast differentiation assays.

Results

Short-term heat pre-treatment did not show any visible effect on hPDL cell morphology, but resulted in a significant downregulation of pro-inflammatory cytokines when being additionally loaded mechanically. Supernatants of heat-exposed hPDL cell cultures demonstrated a reduced impact on monocyte adhesion and osteoclastic differentiation.

Conclusions

Heat pre-treatment of hPDL cells induces cell-protective mechanisms towards mechanical stress and favors the reduction of cell stress associated effects on monocyte/macrophage physiology.

Clinical relevance

These data present the induction of heat shock proteins as a promising treatment option to limit undesired side effects of periodontal remodeling.

Jagodzinski M, Hankemeier S, van Griensven M, Bosch U, Krettek C, Zeichen J (2006) Influence of cyclic mechanical strain and heat of human tendon fibroblasts on HSP-72. Eur J Appl Physiol 96:249–256CrossRefPubMed

Schlesinger MJ (1986) Heat shock proteins: the search for functions. J Cell Biol 103:321–325CrossRefPubMed

Knowlton AA (1995) The role of heat shock proteins in the heart. J Mol Cell Cardiol 27:121–131CrossRefPubMed

Larson JS, Schuetz TJ, Kingston RE (1995) In vitro activation of purified human heat shock factor by heat. Biochemistry 34:1902–1911CrossRefPubMed

Collier NC, Schlesinger MJ (1986) The dynamic state of heat shock proteins in chicken embryo fibroblasts. J Cell Biol 103:1495–1507CrossRefPubMed

Huang WJ, Xia LM, Zhu F, Huang B, Zhou C, Zhu HF, Wang B, Chen B, Lei P, Shen GX (2009) Transcriptional upregulation of HSP70-2 by HIF-1 in cancer cells in response to hypoxia. Int J Cancer 124:298–305CrossRefPubMed

Wong HR, Ryan M, Menendez IY, Denenberg A, Wispe JR (1997) Heat shock protein induction protects human respiratory epithelium against nitric oxide-mediated cytotoxicity. Shock 8:213–218CrossRefPubMed

Wong HR, Ryan M, Wispe JR (1997) The heat shock response inhibits inducible nitric oxide synthase gene expression by blocking I kappa-B degradation and NF-kappa B nuclear translocation. Biochem Biophys Res Commun 231:257–263CrossRefPubMed

Jäger A, Radlanski RJ, Götz W (1993) Demonstration of cells of the mononuclear phagocyte lineage in the periodontium following experimental tooth movement in the rat. An immunohistochemical study using monoclonal antibodies ED1 und ED2 on paraffin-embedded tissues. Histochemistry 100:161–166CrossRefPubMed

10.

Kim YS, Lee YM, Park JS, Lee SK, Kim EC (2010) SIRT1 modulates high-mobility group box 1-induced osteoclastogenic cytokines in human periodontal ligament cells. J Cell Biochem 111:1310–1320CrossRefPubMed

11.

Taniguchi N, Yoshida K, Ito T, Tsuda M, Mishima Y, Furumatsu T, Ronfani L, Abeyama K, Kawahara K, Komiya S, Maruyama I, Lotz M, Bianchi ME, Asahara H (2007) Stage-specific secretion of HMGB1 in cartilage regulates endochondral ossification. Mol Cell Biol 27:5650–5663CrossRefPubMedPubMedCentral

12.

Schiraldi M, Raucci A, Munoz LM, Livoti E, Celona B, Venereau E, Apuzzo T, De Marchis F, Pedotti M, Bachi A, Thelen M, Varani L, Mellado M, Proudfoot A, Bianchi ME, Uguccioni M (2012) HMGB1 promotes recruitment of inflammatory cells to damaged tissues by forming a complex with CXCL12 and signaling via CXCR4. J Exp Med 209:551–563CrossRefPubMedPubMedCentral

13.

Venereau E, Schiraldi M, Uguccioni M, Bianchi ME (2013) HMGB1 and leukocyte migration during trauma and sterile inflammation. Mol Immunol 55:76–82CrossRefPubMed

14.

Wahamaa H, Schierbeck H, Hreggvidsdottir HS, Palmblad K, Aveberger AC, Andersson U, Harris HE (2011) High mobility group box protein 1 in complex with lipopolysaccharide or IL-1 promotes an increased inflammatory phenotype in synovial fibroblasts. Arthritis Res Ther 13:R136CrossRefPubMedPubMedCentral

15.

Garlet TP, Coelho U, Repeke CE, Silva JS, Cunha Fde Q, Garlet GP (2008) Differential expression of osteoblast and osteoclast chemoattractants in compression and tension sides during orthodontic movement. Cytokine 42:330–335CrossRefPubMed

16.

Koide M, Kinugawa S, Takahashi N, Udagawa N (2010) Osteoclastic bone resorption induced by innate immune responses. Periodontol 54:235–246CrossRef

17.

Yamaguchi M, Aihara N, Kojima T, Kasai K (2006) RANKL increase in compressed periodontal ligament cells from root resorption. J Dent Res 85:751–756CrossRefPubMed

18.

Basdra EK, Komposch G (1997) Osteoblast-like properties of human periodontal ligament cells: an in vitro analysis. Eur J Orthod 19:615–621CrossRefPubMed

19.

Ivanovski S, Li H, Haase HR, Bartold PM (2001) Expression of bone associated macromolecules by gingival and periodontal ligament fibroblasts. J Periodontal Res 36:131–141CrossRefPubMed

20.

Chou AM, Sae-Lim V, Lim T, Schantz J, Teoh S, Chew A, al. e (2002) Culturing and characterization of human periodontal ligament fibroblasts-a preliminary study. Mater Sci Eng 20:77–83

21.

Konermann A, Gotz W, Wohlleber D, Knolle P, Deschner J, Jager A (2012) Osteoimmunological mechanisms involved in orthodontically and bacterially induced periodontal stress. J Orofac Orthop 73:430–439CrossRefPubMed

22.

Garlet TP, Coelho U, Silva JS, Garlet GP (2007) Cytokine expression pattern in compression and tension sides of the periodontal ligament during orthodontic tooth movement in humans. Eur J Oral Sci 115:355–362CrossRefPubMed

23.

Konermann A, Beyer M, Deschner J, Allam JP, Novak N, Winter J, Jepsen S, Jager A (2012) Human periodontal ligament cells facilitate leukocyte recruitment and are influenced in their immunomodulatory function by Th17 cytokine release. Cell Immunol 272:137–143CrossRefPubMed

24.

Konermann A, Deschner J, Allam JP, Novak N, Winter J, Baader SL, Jepsen S, Jager A (2012) Antigen-presenting cell marker expression and phagocytotic activity in periodontal ligament cells. J Oral Pathol Med 41:340–347CrossRefPubMed

25.

Konermann A, Stabenow D, Knolle PA, Held SA, Deschner J, Jager A (2012) Regulatory role of periodontal ligament fibroblasts for innate immune cell function and differentiation. Innate Immun March 18:745–752CrossRef

26.

Wolf M, Lossdorfer S, Abuduwali N, Jager A (2013) Potential role of high mobility group box protein 1 and intermittent PTH (1-34) in periodontal tissue repair following orthodontic tooth movement in rats. Clin Oral Investig 17:989–997CrossRefPubMed

27.

Wolf M, Lossdorfer S, Abuduwali N, Meyer R, Kebir S, Gotz W, Jager A (2013) In vivo differentiation of human periodontal ligament cells leads to formation of dental hard tissue. J Orofac Orthop 74:494–505CrossRefPubMed

28.

Wolf M, Lossdorfer S, Craveiro R, Gotz W, Jager A (2013) Regulation of macrophage migration and activity by high-mobility group box 1 protein released from periodontal ligament cells during orthodontically induced periodontal repair: an in vitro and in vivo experimental study. J Orofac Orthop 74:420–434CrossRefPubMed

29.

Wolf M, Lossdorfer S, Craveiro R, Jager A (2014) High-mobility group box protein-1 released by human-periodontal ligament cells modulates macrophage migration and activity in vitro. Innate Immun 20:688–696CrossRefPubMed

30.

Wolf M, Lossdorfer S, Kupper K, Jager A (2014) Regulation of high mobility group box protein 1 expression following mechanical loading by orthodontic forces in vitro and in vivo. Eur J Orthod 36:624–631CrossRefPubMed

31.

Kanzaki H, Chiba M, Arai K, Takahashi I, Haruyama N, Nishimura M, Mitani H (2006) Local RANKL gene transfer to the periodontal tissue accelerates orthodontic tooth movement. Gene Ther 13:678–685CrossRefPubMed

32.

Kanzaki H, Chiba M, Sato A, Miyagawa A, Arai K, Nukatsuka S, Mitani H (2006) Cyclical tensile force on periodontal ligament cells inhibits osteoclastogenesis through OPG induction. J Dent Res 85:457–462CrossRefPubMed

33.

Pinkerton MN, Wescott DC, Gaffey BJ, Beggs KT, Milne TJ, Meikle MC (2008) Cultured human periodontal ligament cells constitutively express multiple osteotropic cytokines and growth factors, several of which are responsive to mechanical deformation. J Periodontal Res 43:343–351CrossRefPubMed

34.

Nakao K, Goto T, Gunjigake KK, Konoo T, Kobayashi S, Yamaguchi K (2007) Intermittent force induces high RANKL expression in human periodontal ligament cells. J Dent Res 86:623–628CrossRefPubMed

35.

Kanzaki H, Chiba M, Shimizu Y, Mitani H (2002) Periodontal ligament cells under mechanical stress induce osteoclastogenesis by receptor activator of nuclear factor kappaB ligand up-regulation via prostaglandin E2 synthesis. J Bone Miner Res 17:210–220CrossRefPubMed

36.

Kim T, Handa A, Iida J, Yoshida S (2007) RANKL expression in rat periodontal ligament subjected to a continuous orthodontic force. Arch Oral Biol 52:244–250CrossRefPubMed

37.

Arai C, Nomura Y, Ishikawa M, Noda K, Choi JW, Yashiro Y, Hanada N, Nakamura Y (2010) HSPA1A is upregulated in periodontal ligament at early stage of tooth movement in rats. Histochem Cell Biol 134:337–343CrossRefPubMed

38.

Hasegawa A, Iwasaka H, Hagiwara S, Noguchi T (2011) Relationship between HMGB1 and tissue protective effects of HSP72 in a LPS-induced systemic inflammation model. J Surg Res 169:85–91CrossRefPubMed

39.

Lossdorfer S, Gotz W, Jager A (2005) PTH(1-34) affects osteoprotegerin production in human PDL cells in vitro. J Dent Res 84:634–638CrossRefPubMed

40.

Lossdörfer S, Götz W, Jäger A (2011) PTH(1-34)-induced changes in RANKL and OPG expression by human PDL cells modify osteoclast biology in a co-culture model with RAW 264.7 cells. Clin Oral Investig 15:941–952CrossRefPubMed

41.

Tang D, Kang R, Xiao W, Jiang L, Liu M, Shi Y, Wang K, Wang H, Xiao X (2007) Nuclear heat shock protein 72 as a negative regulator of oxidative stress (hydrogen peroxide)-induced HMGB1 cytoplasmic translocation and release. J Immunol 178:7376–7384CrossRefPubMedPubMedCentral

42.

Tang D, Kang R, Xiao W, Wang H, Calderwood SK, Xiao X (2007) The anti-inflammatory effects of heat shock protein 72 involve inhibition of high-mobility-group box 1 release and proinflammatory function in macrophages. J Immunol 179:1236–1244CrossRefPubMedPubMedCentral

43.

Winning S, Splettstoesser F, Fandrey J, Frede S (2010) Acute hypoxia induces HIF-independent monocyte adhesion to endothelial cells through increased intercellular adhesion molecule-1 expression: the role of hypoxic inhibition of prolyl hydroxylase activity for the induction of NF-kappa B. J Immunol 185:1786–1793CrossRefPubMed

44.

Barka T, Anderson P (1962) Histochemical methods for acid phosphatase using hexazonium as a coupler. J Histochem Cytochem 10:741–753CrossRef

45.

Luo X, Zuo X, Zhou Y, Zhang B, Shi Y, Liu M, Wang K, McMillian DR, Xiao X (2008) Extracellular heat shock protein 70 inhibits tumour necrosis factor-alpha induced proinflammatory mediator production in fibroblast-like synoviocytes. Arthritis Res Ther 10:R41CrossRefPubMedPubMedCentral

46.

Kramer I, Keller H, Leupin O, Kneissel M (2010) Does osteocytic SOST suppression mediate PTH bone anabolism? Trends Endocrinol Metab 21:237–244CrossRefPubMed

47.

McAteer ME, Niziolek PJ, Ellis SN, Alge DL, Robling AG (2010) Mechanical stimulation and intermittent parathyroid hormone treatment induce disproportional osteogenic, geometric, and biomechanical effects in growing mouse bone. Calcif Tissue Int 86:389–396CrossRefPubMedPubMedCentral

48.

Barkhausen T, van Griensven M, Zeichen J, Bosch U (2003) Modulation of cell functions of human tendon fibroblasts by different repetitive cyclic mechanical stress patterns. Exp Toxicol Pathol 55:153–158CrossRefPubMed

49.

Nollen EA, Brunsting JF, Roelofsen H, Weber LA, Kampinga HH (1999) In vivo chaperone activity of heat shock protein 70 and thermotolerance. Mol Cell Biol 19:2069–2079CrossRefPubMedPubMedCentral

Title: Short-term heat pre-treatment modulates the release of HMGB1 and pro-inflammatory cytokines in hPDL cells following mechanical loading and affects monocyte behavior
Authors: Michael Wolf
Stefan Lossdörfer
Piero Römer
Christian Kirschneck
Katharina Küpper
James Deschner
Andreas Jäger
Publication date: 01-06-2016
Publisher: Springer Berlin Heidelberg
Published in: Clinical Oral Investigations / Issue 5/2016
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI: https://doi.org/10.1007/s00784-015-1580-7

At a glance: The STEP trials

Springer Medicine

Short-term heat pre-treatment modulates the release of HMGB1 and pro-inflammatory cytokines in hPDL cells following mechanical loading and affects monocyte behavior

Abstract

Objective

Materials and methods

Results

Conclusions

Clinical relevance

At a glance: The STEP trials

Springer Medicine

Abstract

Objective

Materials and methods

Results

Conclusions

Clinical relevance

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