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Erschienen in: Immunologic Research 1/2011

01.10.2011

Immunologically restricted patients exhibit a pronounced inflammation and inadequate response to hypoxia in fracture hematomas

verfasst von: Paula Hoff, T. Gaber, K. Schmidt-Bleek, U. Sentürk, C. L. Tran, K. Blankenstein, S. Lütkecosmann, J. Bredahl, H. J. Schüler, P. Simon, G. Wassilew, F. Unterhauser, G. R. Burmester, G. Schmidmaier, C. Perka, G. N. Duda, F. Buttgereit

Erschienen in: Immunologic Research | Ausgabe 1/2011

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Abstract

For patients who are known to have an impaired immune system, bone healing is often impaired. Therefore, it has been suggested that an effectively functioning immune system will have an influence on the quality of bone healing. Here, we demonstrate that cells within the fracture hematoma of immunologically restricted patients (1) exhibit a disturbed osteogenic differentiation (normal SPP1 but diminished RUNX2 expression), (2) show a strong inflammatory reaction (high IL8 and CXCR4), and (3) react on local hypoxia (high expression of HIF1A) but with inadequate target gene responses (diminished LDHA and PGK1 expression). Thus, it is already within the early inflammatory phase of fracture healing that the local gene expression in fracture hematomas of immunologically restricted patients points toward a critical regeneration.
Literatur
1.
Zurück zum Zitat Schmidmaier G, Schwabe P, Wildemann B, Haas NP. Use of bone morphogenetic proteins for treatment of non-unions and future perspectives. Injury. 2007;38(Suppl 4):S35–41.PubMedCrossRef Schmidmaier G, Schwabe P, Wildemann B, Haas NP. Use of bone morphogenetic proteins for treatment of non-unions and future perspectives. Injury. 2007;38(Suppl 4):S35–41.PubMedCrossRef
2.
Zurück zum Zitat Taguchi K, Ogawa R, Migita M, Hanawa H, Ito H, Orimo H. The role of bone marrow-derived cells in bone fracture repair in a green fluorescent protein chimeric mouse model. Biochem Biophys Res Commun. 2005;331:31–6.PubMedCrossRef Taguchi K, Ogawa R, Migita M, Hanawa H, Ito H, Orimo H. The role of bone marrow-derived cells in bone fracture repair in a green fluorescent protein chimeric mouse model. Biochem Biophys Res Commun. 2005;331:31–6.PubMedCrossRef
3.
4.
Zurück zum Zitat Schindeler A, McDonald MM, Bokko P, Little DG. Bone remodeling during fracture repair: the cellular picture. Semin Cell Dev Biol. 2008;19:459–66.PubMedCrossRef Schindeler A, McDonald MM, Bokko P, Little DG. Bone remodeling during fracture repair: the cellular picture. Semin Cell Dev Biol. 2008;19:459–66.PubMedCrossRef
5.
Zurück zum Zitat Kolar P, Schmidt-Bleek K, Schell H, Gaber T, Toben D, Schmidmaier G, Perka C, Buttgereit F, Duda GN. The early fracture hematoma and its potential role in fracture healing. Tissue Eng Part B Rev. 2010;16:427–34.PubMedCrossRef Kolar P, Schmidt-Bleek K, Schell H, Gaber T, Toben D, Schmidmaier G, Perka C, Buttgereit F, Duda GN. The early fracture hematoma and its potential role in fracture healing. Tissue Eng Part B Rev. 2010;16:427–34.PubMedCrossRef
6.
Zurück zum Zitat Gaber T, Dziurla R, Tripmacher R, Burmester GR, Buttgereit F. Hypoxia inducible factor (HIF) in rheumatology: low O2! See what HIF can do!. Ann Rheum Dis. 2005;64:971–80.PubMedCrossRef Gaber T, Dziurla R, Tripmacher R, Burmester GR, Buttgereit F. Hypoxia inducible factor (HIF) in rheumatology: low O2! See what HIF can do!. Ann Rheum Dis. 2005;64:971–80.PubMedCrossRef
7.
Zurück zum Zitat Cramer T, Yamanishi Y, Clausen BE, Forster I, Pawlinski R, Mackman N, Haase VH, Jaenisch R, Corr M, Nizet V, Firestein GS, Gerber HP, Ferrara N, Johnson RS. HIF-1alpha is essential for myeloid cell-mediated inflammation. Cell. 2003;112:645–57.PubMedCrossRef Cramer T, Yamanishi Y, Clausen BE, Forster I, Pawlinski R, Mackman N, Haase VH, Jaenisch R, Corr M, Nizet V, Firestein GS, Gerber HP, Ferrara N, Johnson RS. HIF-1alpha is essential for myeloid cell-mediated inflammation. Cell. 2003;112:645–57.PubMedCrossRef
8.
Zurück zum Zitat Gaber T, Haupl T, Sandig G, Tykwinska K, Fangradt M, Tschirschmann M, Hahne M, Dziurla R, Erekul K, Lautenbach M, Kolar P, Burmester GR, Buttgereit F. Adaptation of human CD4+ T cells to pathophysiological hypoxia: a transcriptome analysis. J Rheumatol. 2009;36:2655–69.PubMedCrossRef Gaber T, Haupl T, Sandig G, Tykwinska K, Fangradt M, Tschirschmann M, Hahne M, Dziurla R, Erekul K, Lautenbach M, Kolar P, Burmester GR, Buttgereit F. Adaptation of human CD4+ T cells to pathophysiological hypoxia: a transcriptome analysis. J Rheumatol. 2009;36:2655–69.PubMedCrossRef
9.
Zurück zum Zitat Epari DR, Kassi JP, Schell H, Duda GN. Timely fracture-healing requires optimization of axial fixation stability. J Bone Joint Surg Am. 2007;89:1575–85.PubMedCrossRef Epari DR, Kassi JP, Schell H, Duda GN. Timely fracture-healing requires optimization of axial fixation stability. J Bone Joint Surg Am. 2007;89:1575–85.PubMedCrossRef
10.
Zurück zum Zitat Lienau J, Schell H, Epari DR, Schutze N, Jakob F, Duda GN, Bail HJ. CYR61 (CCN1) protein expression during fracture healing in an ovine tibial model and its relation to the mechanical fixation stability. J Orthop Res. 2006;24:254–62.PubMedCrossRef Lienau J, Schell H, Epari DR, Schutze N, Jakob F, Duda GN, Bail HJ. CYR61 (CCN1) protein expression during fracture healing in an ovine tibial model and its relation to the mechanical fixation stability. J Orthop Res. 2006;24:254–62.PubMedCrossRef
11.
Zurück zum Zitat Bogoch ER, Moran EL. Bone abnormalities in the surgical treatment of patients with rheumatoid arthritis. Clin Orthop Relat Res. 1999;366:8–21.PubMedCrossRef Bogoch ER, Moran EL. Bone abnormalities in the surgical treatment of patients with rheumatoid arthritis. Clin Orthop Relat Res. 1999;366:8–21.PubMedCrossRef
12.
Zurück zum Zitat Dominiak B, Oxberry W, Chen P. Study on a nonhealing fracture from a patient with systemic lupus erythematosus and its pathogenetic mechanisms. Ultrastruct Pathol. 2005;29:107–20.PubMedCrossRef Dominiak B, Oxberry W, Chen P. Study on a nonhealing fracture from a patient with systemic lupus erythematosus and its pathogenetic mechanisms. Ultrastruct Pathol. 2005;29:107–20.PubMedCrossRef
13.
Zurück zum Zitat Follak N, Kloting I, Merk H. Influence of diabetic metabolic state on fracture healing in spontaneously diabetic rats. Diabetes Metab Res Rev. 2005;21:288–96.PubMedCrossRef Follak N, Kloting I, Merk H. Influence of diabetic metabolic state on fracture healing in spontaneously diabetic rats. Diabetes Metab Res Rev. 2005;21:288–96.PubMedCrossRef
14.
Zurück zum Zitat Kidder LS, Chen X, Schmidt AH, Lew WD. Osteogenic protein-1 overcomes inhibition of fracture healing in the diabetic rat: a pilot study. Clin Orthop Relat Res. 2009;467:3249–56.PubMedCrossRef Kidder LS, Chen X, Schmidt AH, Lew WD. Osteogenic protein-1 overcomes inhibition of fracture healing in the diabetic rat: a pilot study. Clin Orthop Relat Res. 2009;467:3249–56.PubMedCrossRef
15.
16.
Zurück zum Zitat Tyndall WA, Beam HA, Zarro C, O’Connor JP, Lin SS. Decreased platelet derived growth factor expression during fracture healing in diabetic animals. Clin Orthop Relat Res 2003;408:319–30.PubMedCrossRef Tyndall WA, Beam HA, Zarro C, O’Connor JP, Lin SS. Decreased platelet derived growth factor expression during fracture healing in diabetic animals. Clin Orthop Relat Res 2003;408:319–30.PubMedCrossRef
17.
Zurück zum Zitat Kolar P, Gaber T, Perka C, Duda GN, Buttgereit F. Human early fracture hematoma is characterized by inflammation and hypoxia. Clin Orthop Relat Res. 2011. Epub ahead of print. Kolar P, Gaber T, Perka C, Duda GN, Buttgereit F. Human early fracture hematoma is characterized by inflammation and hypoxia. Clin Orthop Relat Res. 2011. Epub ahead of print.
18.
Zurück zum Zitat Busti AJ, Hooper JS, Amaya CJ, Kazi S. Effects of perioperative antiinflammatory and immunomodulating therapy on surgical wound healing. Pharmacotherapy. 2005;25:1566–91.PubMedCrossRef Busti AJ, Hooper JS, Amaya CJ, Kazi S. Effects of perioperative antiinflammatory and immunomodulating therapy on surgical wound healing. Pharmacotherapy. 2005;25:1566–91.PubMedCrossRef
19.
Zurück zum Zitat Chidrawar SM, Khan N, Chan YL, Nayak L, Moss PA. Ageing is associated with a decline in peripheral blood CD56bright NK cells. Immun Ageing. 2006;3:10.PubMedCrossRef Chidrawar SM, Khan N, Chan YL, Nayak L, Moss PA. Ageing is associated with a decline in peripheral blood CD56bright NK cells. Immun Ageing. 2006;3:10.PubMedCrossRef
20.
Zurück zum Zitat Ishikawa M, Nishioka M, Hanaki N, Miyauchi T, Kashiwagi Y, Kawasaki Y, Miki H, Kagawa H, Ioki H, Nakamura Y. Postoperative host responses in elderly patients after gastrointestinal surgery. Hepatogastroenterology. 2006;53:730–5.PubMed Ishikawa M, Nishioka M, Hanaki N, Miyauchi T, Kashiwagi Y, Kawasaki Y, Miki H, Kagawa H, Ioki H, Nakamura Y. Postoperative host responses in elderly patients after gastrointestinal surgery. Hepatogastroenterology. 2006;53:730–5.PubMed
22.
Zurück zum Zitat Woodland DL, Blackman MA. Immunity and age: living in the past? Trends Immunol. 2006;27:303–7.PubMedCrossRef Woodland DL, Blackman MA. Immunity and age: living in the past? Trends Immunol. 2006;27:303–7.PubMedCrossRef
23.
Zurück zum Zitat Kang SC, Matsutani T, Choudhry MA, Schwacha MG, Rue LW, Bland KI, Chaudry IH. Are the immune responses different in middle-aged and young mice following bone fracture, tissue trauma and hemorrhage? Cytokine. 2004;26:223–30.PubMedCrossRef Kang SC, Matsutani T, Choudhry MA, Schwacha MG, Rue LW, Bland KI, Chaudry IH. Are the immune responses different in middle-aged and young mice following bone fracture, tissue trauma and hemorrhage? Cytokine. 2004;26:223–30.PubMedCrossRef
24.
Zurück zum Zitat Arason GJ, Jorgensen GH, Ludviksson BR. Primary immunodeficiency and autoimmunity: lessons from human diseases. Scand J Immunol. 2010;71:317–28.PubMedCrossRef Arason GJ, Jorgensen GH, Ludviksson BR. Primary immunodeficiency and autoimmunity: lessons from human diseases. Scand J Immunol. 2010;71:317–28.PubMedCrossRef
25.
Zurück zum Zitat Yu D, Vinuesa CG. Multiple checkpoints keep follicular helper T cells under control to prevent autoimmunity. Cell Mol Immunol. 2010;7:198–203.PubMedCrossRef Yu D, Vinuesa CG. Multiple checkpoints keep follicular helper T cells under control to prevent autoimmunity. Cell Mol Immunol. 2010;7:198–203.PubMedCrossRef
Metadaten
Titel
Immunologically restricted patients exhibit a pronounced inflammation and inadequate response to hypoxia in fracture hematomas
verfasst von
Paula Hoff
T. Gaber
K. Schmidt-Bleek
U. Sentürk
C. L. Tran
K. Blankenstein
S. Lütkecosmann
J. Bredahl
H. J. Schüler
P. Simon
G. Wassilew
F. Unterhauser
G. R. Burmester
G. Schmidmaier
C. Perka
G. N. Duda
F. Buttgereit
Publikationsdatum
01.10.2011
Verlag
Humana Press Inc
Erschienen in
Immunologic Research / Ausgabe 1/2011
Print ISSN: 0257-277X
Elektronische ISSN: 1559-0755
DOI
https://doi.org/10.1007/s12026-011-8235-9

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