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Published in: Clinical Oral Investigations 3/2013

01-04-2013 | Original Article

Potential role of high mobility group box protein 1 and intermittent PTH (1–34) in periodontal tissue repair following orthodontic tooth movement in rats

Authors: M. Wolf, S. Lossdörfer, N. Abuduwali, A. Jäger

Published in: Clinical Oral Investigations | Issue 3/2013

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Abstract

Objectives

Recent studies indicate that high mobility group box protein 1 (HMGB1) can be released by necrotic and damaged cells and functions as an alarmin that is recognized by the innate immune system. Little is known about the role of HMGB1 within the periodontal ligament (PDL). Therefore, we examined HMGB1 expression by PDL cells in vitro and compared the findings to an in vivo model of orthodontically induced tooth root resorption. In addition, we addressed the question of whether a potentially anabolic intermittent administration of parathyroid hormone (iPTH) would modulate the expression of HMGB1.

Materials and methods

In confluent PDL cell cultures, HMGB1 messenger RNA (mRNA) expression was quantified by real-time polymerase chain reaction. In a rat model comprising 25 animals, mechanical loading for 5 days was followed by administration of either iPTH (1–34) systemically or sham injections for up to 56 days. HMGB1 expression was determined by means of immunohistochemistry and histomorphometry.

Results

The in vitro experiments revealed an inhibitory effect of iPTH on basal HMGB1 mRNA expression in confluent PDL cells. In vivo, the mechanical force-induced enhanced HMGB1 protein expression declined time dependently. Intermittent PTH further inhibited HMGB1 expression. The significantly higher basal HMGB1 protein expression in the former compression side was followed by a more pronounced time- and iPTH-dependent decline in the same area.

Conclusions

These data indicate a major role for HMGB1 in the regulation of PDL wound healing following mechanical load-induced tissue injury.

Clinical relevance

The findings point to the potential benefit of iPTH in the attempt to support these immune-associated reparative processes.
Literature
1.
go back to reference Ranzato E, Patrone M, Pedrazzi M et al (2010) Hmgb1 promotes wound healing of 3 T3 mouse fibroblasts via RAGE-dependent ERK1/2 activation. Cell Biochem Biophys 57:9–17PubMedCrossRef Ranzato E, Patrone M, Pedrazzi M et al (2010) Hmgb1 promotes wound healing of 3 T3 mouse fibroblasts via RAGE-dependent ERK1/2 activation. Cell Biochem Biophys 57:9–17PubMedCrossRef
2.
go back to reference Straino S, Di Carlo A, Mangoni A et al (2008) High-mobility group box 1 protein in human and murine skin: involvement in wound healing. J Invest Dermatol 128:1545–1553PubMedCrossRef Straino S, Di Carlo A, Mangoni A et al (2008) High-mobility group box 1 protein in human and murine skin: involvement in wound healing. J Invest Dermatol 128:1545–1553PubMedCrossRef
3.
go back to reference Dumitriu IE, Baruah P, Valentinis B et al (2005) Release of high mobility group box 1 by dendritic cells controls T cell activation via the receptor for advanced glycation end products. J Immunol 174:7506–7515PubMed Dumitriu IE, Baruah P, Valentinis B et al (2005) Release of high mobility group box 1 by dendritic cells controls T cell activation via the receptor for advanced glycation end products. J Immunol 174:7506–7515PubMed
4.
go back to reference Ulloa L, Messmer D (2006) High-mobility group box 1 (HMGB1) protein: friend and foe. Cytokine Growth Factor Rev 17:189–201PubMedCrossRef Ulloa L, Messmer D (2006) High-mobility group box 1 (HMGB1) protein: friend and foe. Cytokine Growth Factor Rev 17:189–201PubMedCrossRef
5.
go back to reference Charoonpatrapong K, Shah R, Robling AG et al (2006) HMGB1 expression and release by bone cells. J Cell Physiol 207:480–490PubMedCrossRef Charoonpatrapong K, Shah R, Robling AG et al (2006) HMGB1 expression and release by bone cells. J Cell Physiol 207:480–490PubMedCrossRef
6.
go back to reference Yang J, Shah R, Robling AG et al (2008) HMGB1 is a bone-active cytokine. J Cell Physiol 214:730–739PubMedCrossRef Yang J, Shah R, Robling AG et al (2008) HMGB1 is a bone-active cytokine. J Cell Physiol 214:730–739PubMedCrossRef
7.
go back to reference Kim YS, Lee YM, Park JS et al (2010) SIRT1 modulates high-mobility group box 1-induced osteoclastogenic cytokines in human periodontal ligament cells. J Cell Biochem 111:1310–1320PubMedCrossRef Kim YS, Lee YM, Park JS et al (2010) SIRT1 modulates high-mobility group box 1-induced osteoclastogenic cytokines in human periodontal ligament cells. J Cell Biochem 111:1310–1320PubMedCrossRef
8.
go back to reference Morimoto Y, Kawahara KI, Tancharoen S et al (2008) Tumor necrosis factor-alpha stimulates gingival epithelial cells to release high mobility-group box 1. J Periodontal Res 43:76–83PubMedCrossRef Morimoto Y, Kawahara KI, Tancharoen S et al (2008) Tumor necrosis factor-alpha stimulates gingival epithelial cells to release high mobility-group box 1. J Periodontal Res 43:76–83PubMedCrossRef
9.
go back to reference Ebe N, Hara-Yokoyama M, Iwasaki K et al (2011) Pocket epithelium in the pathological setting for HMGB1 release. J Dent Res 90:235–240PubMedCrossRef Ebe N, Hara-Yokoyama M, Iwasaki K et al (2011) Pocket epithelium in the pathological setting for HMGB1 release. J Dent Res 90:235–240PubMedCrossRef
10.
go back to reference Feghali K, Iwasaki K, Tanaka K et al (2009) Human gingival fibroblasts release high-mobility group box-1 protein through active and passive pathways. Oral Microbiol Immunol 24:292–298PubMedCrossRef Feghali K, Iwasaki K, Tanaka K et al (2009) Human gingival fibroblasts release high-mobility group box-1 protein through active and passive pathways. Oral Microbiol Immunol 24:292–298PubMedCrossRef
11.
go back to reference Brezniak N, Wasserstein A (2002) Orthodontically induced inflammatory root resorption. Part II: the clinical aspects. Angle Orthod 72:180–184PubMed Brezniak N, Wasserstein A (2002) Orthodontically induced inflammatory root resorption. Part II: the clinical aspects. Angle Orthod 72:180–184PubMed
12.
go back to reference Krishnan V, Davidovitch Z (2006) Cellular, molecular, and tissue-level reactions to orthodontic force. Am J Orthod Dentofacial Orthop 129(469):e1–e32PubMed Krishnan V, Davidovitch Z (2006) Cellular, molecular, and tissue-level reactions to orthodontic force. Am J Orthod Dentofacial Orthop 129(469):e1–e32PubMed
13.
go back to reference Taithongchai R, Sookkorn K, Killiany D (1996) Facial and dentoalveolar structure and the prediction of apical root shortening. Am J Orthod Dentofacial Orthop 110:296–302PubMedCrossRef Taithongchai R, Sookkorn K, Killiany D (1996) Facial and dentoalveolar structure and the prediction of apical root shortening. Am J Orthod Dentofacial Orthop 110:296–302PubMedCrossRef
14.
go back to reference Owman-Moll P, Kurol J (1998) The early reparative process of orthodontically induced root resorption in adolescents—location and type of tissue. Eur J Orthod 20:727–732PubMedCrossRef Owman-Moll P, Kurol J (1998) The early reparative process of orthodontically induced root resorption in adolescents—location and type of tissue. Eur J Orthod 20:727–732PubMedCrossRef
15.
go back to reference Chen SC, Marino V, Gronthos S et al (2006) Location of putative stem cells in human periodontal ligament. J Periodontal Res 41:547–553PubMedCrossRef Chen SC, Marino V, Gronthos S et al (2006) Location of putative stem cells in human periodontal ligament. J Periodontal Res 41:547–553PubMedCrossRef
16.
go back to reference Chou AM, Sae-Lim V, Lim T et al (2002) Culturing and characterization of human periodontal ligament fibroblasts—a preliminary study. Mater Sci Eng 20:77–83CrossRef Chou AM, Sae-Lim V, Lim T et al (2002) Culturing and characterization of human periodontal ligament fibroblasts—a preliminary study. Mater Sci Eng 20:77–83CrossRef
17.
go back to reference Nagatomo K, Komaki M, Sekiya I et al (2006) Stem cell properties of human periodontal ligament cells. J Periodontal Res 41:303–310PubMedCrossRef Nagatomo K, Komaki M, Sekiya I et al (2006) Stem cell properties of human periodontal ligament cells. J Periodontal Res 41:303–310PubMedCrossRef
18.
go back to reference Seo BM, Miura M, Gronthos S et al (2004) Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet 364:149–155PubMedCrossRef Seo BM, Miura M, Gronthos S et al (2004) Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet 364:149–155PubMedCrossRef
19.
go back to reference Trubiani O, Di Primio R, Traini T et al (2005) Morphological and cytofluorimetric analysis of adult mesenchymal stem cells expanded ex vivo from periodontal ligament. Int J Immunopathol Pharmacol 18:213–221PubMed Trubiani O, Di Primio R, Traini T et al (2005) Morphological and cytofluorimetric analysis of adult mesenchymal stem cells expanded ex vivo from periodontal ligament. Int J Immunopathol Pharmacol 18:213–221PubMed
20.
go back to reference Nohutcu RM, Somerman MJ, McCauley LK (1995) Dexamethasone enhances the effects of parathyroid hormone on human periodontal ligament cells in vitro. Calcif Tissue Int 56:571–577PubMedCrossRef Nohutcu RM, Somerman MJ, McCauley LK (1995) Dexamethasone enhances the effects of parathyroid hormone on human periodontal ligament cells in vitro. Calcif Tissue Int 56:571–577PubMedCrossRef
21.
go back to reference Ouyang H, McCauley LK, Berry JE et al (2000) Response of immortalized murine cementoblasts/periodontal ligament cells to parathyroid hormone and parathyroid hormone-related protein in vitro. Arch Oral Biol 45:293–303PubMedCrossRef Ouyang H, McCauley LK, Berry JE et al (2000) Response of immortalized murine cementoblasts/periodontal ligament cells to parathyroid hormone and parathyroid hormone-related protein in vitro. Arch Oral Biol 45:293–303PubMedCrossRef
22.
go back to reference Lekic PC, Rajshankar D, Chen H et al (2001) Transplantation of labeled periodontal ligament cells promotes regeneration of alveolar bone. Anat Rec 262:193–202PubMedCrossRef Lekic PC, Rajshankar D, Chen H et al (2001) Transplantation of labeled periodontal ligament cells promotes regeneration of alveolar bone. Anat Rec 262:193–202PubMedCrossRef
23.
go back to reference Sone T, Fukunaga M, Ono S et al (1995) A small dose of human parathyroid hormone (1–34) increased bone mass in the lumbar vertebrae in patients with senile osteoporosis. Miner Electrolyte Metab 21:232–235PubMed Sone T, Fukunaga M, Ono S et al (1995) A small dose of human parathyroid hormone (1–34) increased bone mass in the lumbar vertebrae in patients with senile osteoporosis. Miner Electrolyte Metab 21:232–235PubMed
24.
go back to reference Verhaar HJ, Lems WF (2010) PTH analogues and osteoporotic fractures. Expert Opin Biol Ther 10:1387–1394PubMedCrossRef Verhaar HJ, Lems WF (2010) PTH analogues and osteoporotic fractures. Expert Opin Biol Ther 10:1387–1394PubMedCrossRef
25.
go back to reference Barros SP, Silva MA, Somerman MJ et al (2003) Parathyroid hormone protects against periodontitis-associated bone loss. J Dent Res 82:791–795PubMedCrossRef Barros SP, Silva MA, Somerman MJ et al (2003) Parathyroid hormone protects against periodontitis-associated bone loss. J Dent Res 82:791–795PubMedCrossRef
26.
go back to reference Marques MR, da Silva MA, Manzi FR et al (2005) Effect of intermittent PTH administration in the periodontitis-associated bone loss in ovariectomized rats. Arch Oral Biol 50:421–429PubMedCrossRef Marques MR, da Silva MA, Manzi FR et al (2005) Effect of intermittent PTH administration in the periodontitis-associated bone loss in ovariectomized rats. Arch Oral Biol 50:421–429PubMedCrossRef
27.
go back to reference Bashutski JD, Eber RM, Kinney JS et al (2010) Teriparatide and osseous regeneration in the oral cavity. N Engl J Med 363:2396–2405PubMedCrossRef Bashutski JD, Eber RM, Kinney JS et al (2010) Teriparatide and osseous regeneration in the oral cavity. N Engl J Med 363:2396–2405PubMedCrossRef
28.
go back to reference Lossdorfer S, Gotz W, Jager A (2005) PTH (1–34) affects osteoprotegerin production in human PDL cells in vitro. J Dent Res 84:634–638PubMedCrossRef Lossdorfer S, Gotz W, Jager A (2005) PTH (1–34) affects osteoprotegerin production in human PDL cells in vitro. J Dent Res 84:634–638PubMedCrossRef
29.
go back to reference Lossdorfer S, Gotz W, Rath-Deschner B et al (2006) Parathyroid hormone (1–34) mediates proliferative and apoptotic signaling in human periodontal ligament cells in vitro via protein kinase C-dependent and protein kinase A-dependent pathways. Cell Tissue Res 325:469–479PubMedCrossRef Lossdorfer S, Gotz W, Rath-Deschner B et al (2006) Parathyroid hormone (1–34) mediates proliferative and apoptotic signaling in human periodontal ligament cells in vitro via protein kinase C-dependent and protein kinase A-dependent pathways. Cell Tissue Res 325:469–479PubMedCrossRef
30.
go back to reference Lossdorfer S, Gotz W, Jager 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 15:941–952PubMedCrossRef Lossdorfer S, Gotz W, Jager 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 15:941–952PubMedCrossRef
31.
go back to reference Lossdörfer S, Kraus D, Abuduwali N et al (2011) Intermittent PTH(1–34) regulates the osteoblastic differentiation of human periodontal ligament cells via protein kinase C- and protein kinase A-dependent pathways in vitro. J Periodontal Res 46:318–326PubMedCrossRef Lossdörfer S, Kraus D, Abuduwali N et al (2011) Intermittent PTH(1–34) regulates the osteoblastic differentiation of human periodontal ligament cells via protein kinase C- and protein kinase A-dependent pathways in vitro. J Periodontal Res 46:318–326PubMedCrossRef
32.
go back to reference Lossdorfer S, Kraus D, Jager A (2010) Aging affects the phenotypic characteristics of human periodontal ligament cells and the cellular response to hormonal stimulation in vitro. J Periodontal Res 45:764–771PubMedCrossRef Lossdorfer S, Kraus D, Jager A (2010) Aging affects the phenotypic characteristics of human periodontal ligament cells and the cellular response to hormonal stimulation in vitro. J Periodontal Res 45:764–771PubMedCrossRef
33.
go back to reference Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods 25:402–408PubMedCrossRef Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods 25:402–408PubMedCrossRef
34.
go back to reference Lossdorfer S, Yildiz F, Gotz W et al (2010) Anabolic effect of intermittent PTH (1–34) on the local microenvironment during the late phase of periodontal repair in a rat model of tooth root resorption. Clin Oral Investig 14:89–98PubMedCrossRef Lossdorfer S, Yildiz F, Gotz W et al (2010) Anabolic effect of intermittent PTH (1–34) on the local microenvironment during the late phase of periodontal repair in a rat model of tooth root resorption. Clin Oral Investig 14:89–98PubMedCrossRef
35.
go back to reference Waldo CM, Rothblatt JM (1954) Histologic response to tooth movement in the laboratory rat; procedure and preliminary observations. J Dent Res 33:481–486PubMedCrossRef Waldo CM, Rothblatt JM (1954) Histologic response to tooth movement in the laboratory rat; procedure and preliminary observations. J Dent Res 33:481–486PubMedCrossRef
36.
go back to reference Sato M, Vahle J, Schmidt A et al (2002) Abnormal bone architecture and biomechanical properties with near-lifetime treatment of rats with PTH. Endocrinology 143:3230–3242PubMedCrossRef Sato M, Vahle J, Schmidt A et al (2002) Abnormal bone architecture and biomechanical properties with near-lifetime treatment of rats with PTH. Endocrinology 143:3230–3242PubMedCrossRef
37.
go back to reference Gotz W, Kunert D, Zhang D et al (2006) Insulin-like growth factor system components in the periodontium during tooth root resorption and early repair processes in the rat. Eur J Oral Sci 114:318–327PubMedCrossRef Gotz W, Kunert D, Zhang D et al (2006) Insulin-like growth factor system components in the periodontium during tooth root resorption and early repair processes in the rat. Eur J Oral Sci 114:318–327PubMedCrossRef
38.
go back to reference Jager A, Kunert D, Friesen T et al (2008) Cellular and extracellular factors in early root resorption repair in the rat. Eur J Orthod 30:336–345PubMedCrossRef Jager A, Kunert D, Friesen T et al (2008) Cellular and extracellular factors in early root resorption repair in the rat. Eur J Orthod 30:336–345PubMedCrossRef
39.
go back to reference Bianchi ME (2007) DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol 81:1–5PubMedCrossRef Bianchi ME (2007) DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol 81:1–5PubMedCrossRef
40.
go back to reference Savill J, Dransfield I, Gregory C et al (2002) A blast from the past: clearance of apoptotic cells regulates immune responses. Nat Rev Immunol 2:965–975PubMedCrossRef Savill J, Dransfield I, Gregory C et al (2002) A blast from the past: clearance of apoptotic cells regulates immune responses. Nat Rev Immunol 2:965–975PubMedCrossRef
41.
go back to reference Gotz W, Lossdorfer S, Kruger U et al (2003) Immunohistochemical localization of insulin-like growth factor-II and its binding protein-6 in human epithelial cells of Malassez. Eur J Oral Sci 111:26–33PubMedCrossRef Gotz W, Lossdorfer S, Kruger U et al (2003) Immunohistochemical localization of insulin-like growth factor-II and its binding protein-6 in human epithelial cells of Malassez. Eur J Oral Sci 111:26–33PubMedCrossRef
42.
go back to reference Meghji S, Qureshi W, Henderson B et al (1996) The role of endotoxin and cytokines in the pathogenesis of odontogenic cysts. Arch Oral Biol 41:523–531PubMedCrossRef Meghji S, Qureshi W, Henderson B et al (1996) The role of endotoxin and cytokines in the pathogenesis of odontogenic cysts. Arch Oral Biol 41:523–531PubMedCrossRef
43.
go back to reference Liu F, Abiko Y, Nishimura M et al (2001) Expression of inflammatory cytokines and beta-defensin 1 mRNAs in porcine epithelial rests of Malassez in vitro. Med Electron Microsc 34:174–178PubMedCrossRef Liu F, Abiko Y, Nishimura M et al (2001) Expression of inflammatory cytokines and beta-defensin 1 mRNAs in porcine epithelial rests of Malassez in vitro. Med Electron Microsc 34:174–178PubMedCrossRef
44.
go back to reference Ohshima M, Nishiyama T, Tokunaga K et al (2000) Profiles of cytokine expression in radicular cyst-lining epithelium examined by RT-PCR. J Oral Sci 42:239–246PubMedCrossRef Ohshima M, Nishiyama T, Tokunaga K et al (2000) Profiles of cytokine expression in radicular cyst-lining epithelium examined by RT-PCR. J Oral Sci 42:239–246PubMedCrossRef
45.
go back to reference Kale S, Kocadereli I, Atilla P et al (2004) Comparison of the effects of 1,25 dihydroxycholecalciferol and prostaglandin E2 on orthodontic tooth movement. Am J Orthod Dentofacial Orthop 125:607–614PubMedCrossRef Kale S, Kocadereli I, Atilla P et al (2004) Comparison of the effects of 1,25 dihydroxycholecalciferol and prostaglandin E2 on orthodontic tooth movement. Am J Orthod Dentofacial Orthop 125:607–614PubMedCrossRef
46.
go back to reference Rincon JC, Young WG, Bartold PM (2006) The epithelial cell rests of Malassez—a role in periodontal regeneration? J Periodontal Res 41:245–252PubMedCrossRef Rincon JC, Young WG, Bartold PM (2006) The epithelial cell rests of Malassez—a role in periodontal regeneration? J Periodontal Res 41:245–252PubMedCrossRef
47.
go back to reference Jager A, Radlanski RJ, Gotz 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 100:161–166PubMedCrossRef Jager A, Radlanski RJ, Gotz 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 100:161–166PubMedCrossRef
48.
Metadata
Title
Potential role of high mobility group box protein 1 and intermittent PTH (1–34) in periodontal tissue repair following orthodontic tooth movement in rats
Authors
M. Wolf
S. Lossdörfer
N. Abuduwali
A. Jäger
Publication date
01-04-2013
Publisher
Springer-Verlag
Published in
Clinical Oral Investigations / Issue 3/2013
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI
https://doi.org/10.1007/s00784-012-0777-2

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