Fracture healing is accelerated in the absence of the adaptive immune system

Journal of Bone and Mineral Research

Volumn 26, Issue 1, 2011, Pages 113-124

  Toben, Daniel ^a,b   Schroeder, Ireen ^a,b   El Khassawna, Thaqif ^a,b   Mehta, Manav ^a,b   Hoffmann, Jan Erik ^a,b   Frisch, Jan Tilmann ^a,b   Schell, Hanna ^a,b   Lienau, Jasmin ^a,b   Serra, Alessandro ^b,c   Radbruch, Andreas ^b,c   Duda, Georg N ^a,b  

^a CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^b Berlin Brandenburg Center for Regenerative Therapies   (Germany)

^c DEUTSCHES RHEUMA FORSCHUNGSZENTRUM   (Germany)

Author keywords

ADAPTIVE IMMUNITY; BONE; FRACTURE HEALING; LYMPHOCYTES; OSTEOIMMUNOLOGY

Indexed keywords

INTERLEUKIN 10; MESSENGER RNA; RAG1 PROTEIN;

ADAPTIVE IMMUNITY; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BIOMECHANICS; BONE MINERALIZATION; BONE REMODELING; CALLUS; CONTROLLED STUDY; ENCHONDRAL OSSIFICATION; FEMUR FRACTURE; FRACTURE HEALING; HEMATOMA; IMMUNOMODULATION; LYMPHOCYTE; MALE; MICRO-COMPUTED TOMOGRAPHY; MORPHOMETRICS; MOUSE; NONHUMAN; PROTEIN EXPRESSION; TORQUE; UPREGULATION;

ADAPTIVE IMMUNITY; ANIMALS; B-LYMPHOCYTES; BIOMECHANICS; BONE REMODELING; BONY CALLUS; CALCIFICATION, PHYSIOLOGIC; CELL DIFFERENTIATION; CYTOKINES; FRACTURE HEALING; HOMEODOMAIN PROTEINS; IMMUNE SYSTEM; INFLAMMATION; MALE; MICE; MICE, INBRED C57BL; OSTEOCLASTS; OSTEOGENESIS; RNA, MESSENGER; T-LYMPHOCYTES; X-RAY MICROTOMOGRAPHY;

EID: 78650938516     PISSN: 08840431     EISSN: None     Source Type: Journal    
DOI: 10.1002/jbmr.185     Document Type: Article

References (59)

1. Einhorn TA., The cell and molecular biology of fracture healing. Clin Orthop Relat Res. 1998; 355: 7s-21.
2. McKibbin B., The biology of fracture healing in long bones. J Bone Joint Surg Br. 1978; 60B: 150-162.
3. Schmidt-Bleek K, Schell H, Kolar P, et al. Cellular composition of the initial fracture hematoma compared to a muscle hematoma: a study in sheep. J Orthop Res. 2009; 27: 1147-1151.
4. Timlin M, Toomey D, Condron C, et al. Fracture hematoma is a potent proinflammatory mediator of neutrophil function. J Trauma. 2005; 58: 1223-1229.
5. Martin P, Leibovich SJ., Inflammatory cells during wound repair: the good, the bad and the ugly. Trends Cell Biol. 2005; 15: 599-607.
6. Kolar P, Schmidt-Bleek K, Schell H, et al. The early fracture hematoma and its potential role in fracture healing. Tissue Eng Part B Rev. 2010; 16: 427-434.
7. Schindeler A, Liu R, Little DG., The contribution of different cell lineages to bone repair: exploring a role for muscle stem cells. Differentiation. 2009; 77: 12-18.
8. Mizuno K, Mineo K, Tachibana T, Sumi M, Matsubara T, Hirohata K., The osteogenetic potential of fracture haematoma. Subperiosteal and intramuscular transplantation of the haematoma. J Bone Joint Surg Br. 1990; 72: 822-829.
9. Ferguson C, Alpern E, Miclau T, Helms JA., Does adult fracture repair recapitulate embryonic skeletal formation ? Mech Dev. 1999; 87: 57-66.
10. Manabe N, Kawaguchi H, Chikuda H, et al. Connection between B lymphocyte and osteoclast differentiation pathways. J Immunol. 2001; 167: 2625-2631.
11. Horwood NJ, Kartsogiannis V, Quinn JM, Romas E, Martin TJ, Gillespie MT., Activated T lymphocytes support osteoclast formation in vitro. Biochem Biophys Res Commun. 1999; 265: 144-150.
12. Lorenzo J, Horowitz M, Choi Y., Osteoimmunology: interactions of the bone and immune system. Endocr Rev. 2008; 29: 403-440.
13. Suh WK, Wang SX, Jheon AH, et al. The immune regulatory protein B7-H3 promotes osteoblast differentiation and bone mineralization. Proc Natl Acad Sci U S A. 2004; 101: 12969-12973.
14. Takayanagi H., Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems. Nat Rev Immunol. 2007; 7: 292-304.
15. Horowitz M, Vignery A, Gershon RK, Baron R., Thymus-derived lymphocytes and their interactions with macrophages are required for the production of osteoclast-activating factor in the mouse. Proc Natl Acad Sci U S A. 1984; 81: 2181-2185.
16. Li J, Sarosi I, Yan XQ, et al. RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism. Proc Natl Acad Sci U S A. 2000; 97: 1566-1571.
17. Gerstenfeld LC, Sacks DJ, Pelis M, et al. Comparison of effects of the bisphosphonate alendronate versus the RANKL inhibitor denosumab on murine fracture healing. J Bone Mine Res. 2009; 24: 196-208.
18. Park JE, Barbul A., Understanding the role of immune regulation in wound healing. Am J Surg. 2004; 187: 11S-16S.
19. Schaffer M, Barbul A., Lymphocyte function in wound healing and following injury. Br J Surg. 1998; 85: 444-460.
20. Schaffer M, Bongartz M, Hoffmann W, Viebahn R., MHC-class-II-deficiency impairs wound healing. J Surg Res. 2007; 138: 100-105.
21. Dimayuga P, Cercek B, Oguchi S, et al. Inhibitory effect on arterial injury-induced neointimal formation by adoptive B-cell transfer in Rag-1 knockout mice. Arterioscler Thromb Vasc Biol. 2002; 22: 644-649.
22. Marusic A, Grcevic D, Katavic V, et al. Role of B lymphocytes in new bone formation. Lab Invest. 2000; 80: 1761-1774.
23. Gaston MS, Noble BS, Simpson HR., Enhanced fracture repair in-vivo in the absence of the specific immune system. Meeting of the Orthopedic Research Society paper. 2007; 357.
24. Holstein JH, Klein M, Garcia P, et al. Rapamycin affects early fracture healing in mice. Br J Pharmacol. 2008; 154: 1055-1062.
25. Mombaerts P, Iacomini J, Johnson RS, Herrup K, Tonegawa S, Papaioannou VE., RAG-1-deficient mice have no mature B and T lymphocytes. Cell. 1992; 68: 869-877.
26. Bonnarens F, Einhorn TA., Production of a standard closed fracture in laboratory animal bone. J Orthop Res. 1984; 2: 97-101.
27. Kakar S, Einhorn TA, Vora S, et al. Enhanced chondrogenesis and Wnt-signaling in parathyroid hormone treated fractures. J Bone Miner Res. 2007; 22: 1903-1912.
28. Hildebrand T, Ruegsegger P., Quantification of bone microarchitecture with the structure model index. Comput Methods Biomech Biomed Engin. 1997; 1: 15-23.
29. Parfitt AM, Drezner MK, Glorieux FH, et al. Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res. 1987; 2: 595-610.
30. Gerstenfeld LC, Wronski TJ, Hollinger JO, Einhorn TA., Application of histomorphometric methods to the study of bone repair. J Bone Miner Res. 2005; 20: 1715-1722.
31. Peters A, Toben D, Lienau J, et al. Locally applied osteogenic pre-differentiated progenitor cells are more effective than undifferentiated mesenchymal stem cells in the treatment of delayed bone healing. Tissue Eng Part A. 2009; 15: 2947-2954.
32. Cho TJ, Gerstenfeld LC, Einhorn TA., Differential temporal expression of members of the transforming growth factor beta superfamily during murine fracture healing. J Bone Miner Res. 2002; 17: 513-520.
33. Kaback LA, Soung do Y, Naik A, et al. Osterix/Sp7 regulates mesenchymal stem cell mediated endochondral ossification. J Cell Physiol. 2008; 214: 173-182.
34. Huston DP., The biology of the immune system. JAMA. 1997; 278: 1804-1814.
35. Colburn NT, Zaal KJ, Wang F, Tuan RS., A role for gamma/delta T cells in a mouse model of fracture healing. Arthritis Rheum. 2009; 60: 1694-1703.
36. Sato K, Suematsu A, Okamoto K, et al. Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction. J Exp Med. 2006; 203: 2673-2682.
37. Murphy TJ, Ni Choileain N, Zang Y, Mannick JA, Lederer JA., CD4+CD25+ regulatory T cells control innate immune reactivity after injury. J Immunol. 2005; 174: 2957-2963.
38. Weitzmann MN, Cenci S, Rifas L, Haug J, Dipersio J, Pacifici R., T cell activation induces human osteoclast formation via receptor activator of nuclear factor kappaB ligand-dependent and -independent mechanisms. J Bone Miner Res. 2001; 16: 328-337.
39. Zaiss MM, Axmann R, Zwerina J, et al. Treg cells suppress osteoclast formation: a new link between the immune system and bone. Arthritis Rheum. 2007; 56: 4104-4112.
40. Zhou FH, Foster BK, Zhou XF, Cowin AJ, Xian CJ., TNF-alpha mediates p38 MAP kinase activation and negatively regulates bone formation at the injured growth plate in rats. J Bone Miner Res. 2006; 21: 1075-1088.
41. Feldmann M, Maini RN., Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned ? Annu Rev Immunol. 2001; 19: 163-196.
42. Ochi H, Hara Y, Tagawa M, Shinomiya K, Asou Y., The roles of TNFR1 in lipopolysaccharide-induced bone loss: dual effects of TNFR1 on bone metabolism via osteoclastogenesis and osteoblast survival. J Orthop Res. 28: 657-663.
43. Gerstenfeld LC, Cho TJ, Kon T, et al. Impaired fracture healing in the absence of TNF-alpha signaling: the role of TNF-alpha in endochondral cartilage resorption. J Bone Miner Res. 2003; 18: 1584-1592.
44. Lehmann W, Edgar CM, Wang K, et al. Tumor necrosis factor alpha (TNF-alpha) coordinately regulates the expression of specific matrix metalloproteinases (MMPS) and angiogenic factors during fracture healing. Bone. 2005; 36: 300-310.
45. Martin-Fontecha A, Thomsen LL, Brett S, et al. Induced recruitment of NK cells to lymph nodes provides IFN-gamma for T(H)1 priming. Nat Immunol. 2004; 5: 1260-1265.
46. Grutz G., New insights into the molecular mechanism of interleukin-10-mediated immunosuppression. J Leukoc Biol. 2005; 77: 3-15.
47. Liu D, Yao S, Wise GE., Effect of interleukin-10 on gene expression of osteoclastogenic regulatory molecules in the rat dental follicle. Eur J Oral Sci. 2006; 114: 42-49.
48. Sasaki H, Hou L, Belani A, et al. IL-10, but not IL-4, suppresses infection-stimulated bone resorption in vivo. J Immunol. 2000; 165: 3626-3630.
49. Dresner-Pollak R, Gelb N, Rachmilewitz D, Karmeli F, Weinreb M., Interleukin 10-deficient mice develop osteopenia, decreased bone formation, and mechanical fragility of long bones. Gastroenterology. 2004; 127: 792-801.
50. Einhorn TA, Majeska RJ, Rush EB, Levine PM, Horowitz MC., The expression of cytokine activity by fracture callus. J Bone Miner Res. 1995; 10: 1272-1281.
51. Malek TR., The biology of interleukin-2. Annu Rev Immunol. 2008; 26: 453-479.
52. Schneider GB, Relfson M., Effects of interleukin-2 on bone resorption and natural immunity in osteopetrotic (ia) rats. Lymphokine Cytokine Res. 1994; 13: 335-341.
53. Brown MA, Hural J., Functions of IL-4 and control of its expression. Crit Rev Immunol. 1997; 17: 1-32.
54. Howard M, Farrar J, Hilfiker M, et al. Identification of a T cell-derived b cell growth factor distinct from interleukin 2. J Exp Med. 1982; 155: 914-923.
55. Baumann H, Gauldie J., The acute phase response. Immunol Today. 1994; 15: 74-80.
56. Watanabe K, Tanaka Y, Morimoto I, et al. Interleukin-4 as a potent inhibitor of bone resorption. Biochem Biophys Res Commun. 1990; 172: 1035-1041.
57. Lind M, Deleuran B, Yssel H, Fink-Eriksen E, Thestrup-Pedersen K., IL-4 and IL-13, but not IL-10, are chemotactic factors for human osteoblasts. Cytokine. 1995; 7: 78-82.
58. Grundy MA, Sentman CL., Immunodeficient mice have elevated numbers of NK cells in non-lymphoid tissues. Exp Cell Res. 2006; 312: 3920-3926.
59. June CH, Blazar BR, Riley JL., Engineering lymphocyte subsets: tools, trials and tribulations. Nat Rev Immunol. 2009; 9: 704-716.