Biological and molecular profile of fracture non-union tissue: Current insights

Journal of Cellular and Molecular Medicine

Volumn 19, Issue 4, 2015, Pages 685-713

  Panteli, Michalis ^a   Pountos, Ippokratis ^a   Jones, Elena ^a   Giannoudis, Peter V ^a,b  

^a UNIVERSITY OF LEEDS   (United Kingdom)

^b CHAPEL ALLERTON HOSPITAL   (United Kingdom)

Author keywords

Bone morphogenic protein(s); Human tissue; Mesenchymal stem cell(s); Non union(s)

Indexed keywords

ALKALINE PHOSPHATASE; BONE MORPHOGENETIC PROTEIN; LEUKOCYTE ANTIGEN; MATRIX METALLOPROTEINASE; TRANSCRIPTOME;

FRACTURE HEALING; FRACTURE NONUNION; GENETICS; HUMAN; METABOLISM; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; WESTERN BLOTTING;

ALKALINE PHOSPHATASE; ANTIGENS, CD; BLOTTING, WESTERN; BONE MORPHOGENETIC PROTEINS; FRACTURE HEALING; FRACTURES, UNUNITED; HUMANS; MATRIX METALLOPROTEINASES; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; TRANSCRIPTOME;

EID: 84925937688     PISSN: 15821838     EISSN: None     Source Type: Journal    
DOI: 10.1111/jcmm.12532     Document Type: Article

References (64)

1. Ferguson C, Alpern E, Miclau T, et al. Does adult fracture repair recapitulate embryonic skeletal formation? Mech Dev. 1999; 87: 57-66.
2. Komatsu DE, Warden SJ. The control of fracture healing and its therapeutic targeting: improving upon nature. J Cell Biochem. 2010; 109: 302-11.
3. Giannoudis PV, Einhorn TA, Marsh D. Fracture healing: the diamond concept. Injury. 2007; 38: S3-6.
4. Schroeder JE, Mosheiff R. Tissue engineering approaches for bone repair: concepts and evidence. Injury. 2011; 42: 609-13.
5. Giannoudis PV, Panteli M, Calori GM. Bone healing: the diamond concept. In: Bentley G, editor. European Instructional Lectures. Berlin, Heidelberg: Springer; 2014. pp. 3-16.
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: 427-34.
7. Dimitriou R, Tsiridis E, Giannoudis PV. Current concepts of molecular aspects of bone healing. Injury. 2005; 36: 1392-404.
8. Henle P, Zimmermann G, Weiss S. Matrix metalloproteinases and failed fracture healing. Bone. 2005; 37: 791-8.
9. Tsiridis E, Upadhyay N, Giannoudis P. Molecular aspects of fracture healing: which are the important molecules? Injury. 2007; 38: S11-25.
10. Sarahrudi K, Thomas A, Mousavi M, et al. Elevated transforming growth factor-beta 1 (TGF-beta1) levels in human fracture healing. Injury. 2011; 42: 833-7.
11. Giannoudis PV, Ahmad MA, Mineo GV, et al. Subtrochanteric fracture non-unions with implant failure managed with the "Diamond" concept. Injury. 2013; 44(Suppl. 1): S76-81.
12. Einhorn TA. The science of fracture healing. J Orthop Trauma. 2005; 19: S4-6.
13. Phillips AM. Overview of the fracture healing cascade. Injury. 2005; 36: S5-7.
14. Fajardo M, Liu CJ, Ilalov K, et al. Matrix metalloproteinases that associate with and cleave bone morphogenetic protein-2 in vitro are elevated in hypertrophic fracture nonunion tissue. J Orthop Trauma. 2010; 24: 557-63.
15. Marsell R, Einhorn TA. The biology of fracture healing. Injury. 2011; 42: 551-5.
16. Carano RA, Filvaroff EH. Angiogenesis and bone repair. Drug Discovery Today. 2003; 8: 980-9.
17. Einhorn TA. The cell and molecular biology of fracture healing. Clin Orthop Relat Res. 1998; (355 Suppl): S7-21.
18. Koga T, Lee SY, Niikura T, et al. Effect of low-intensity pulsed ultrasound on bone morphogenetic protein 7-induced osteogenic differentiation of human nonunion tissue-derived cells in vitro. J Ultrasound Med. 2013; 32: 915-22.
19. Lawton DM, Andrew JG, Marsh DR, et al. Expression of the gene encoding the matrix gla protein by mature osteoblasts in human fracture non-unions. Molecular pathology. 1999; 52: 92-6.
20. Lombardi G, Perego S, Luzi L, et al. A four-season molecule: osteocalcin. Updates in its physiological roles. Endocrine. 2015; 48: 394-404.
21. Monfoulet L, Malaval L, Aubin JE, et al. Bone sialoprotein, but not osteopontin, deficiency impairs the mineralization of regenerating bone during cortical defect healing. Bone. 2010; 46: 447-52.
22. Zimmermann G, Schmeckenbecher KH, Boeuf S, et al. Differential gene expression analysis in fracture callus of patients with regular and failed bone healing. Injury. 2012; 43: 347-56.
23. Pountos I, Panteli M, Panagiotopoulos E, et al. Can we enhance fracture vascularity: what is the evidence? Injury. 2014; 45: S49-57.
24. Bhandari M, Guyatt GH, Swiontkowski MF, et al. A lack of consensus in the assessment of fracture healing among orthopaedic surgeons. J Orthop Trauma. 2002; 16: 562-6.
25. Bishop JA, Palanca AA, Bellino MJ, et al. Assessment of compromised fracture healing. J Am Acad Orthop Surg. 2012; 20: 273-82.
26. Nauth A, Miclau T 3rd, Li R, et al. Gene therapy for fracture healing. J Orthop Trauma. 2010; 24: S17-24.
27. Kanakaris NK, Giannoudis PV. The health economics of the treatment of long-bone non-unions. Injury. 2007; 38: S77-84.
28. Sarmiento A, Sharpe FE, Ebramzadeh E, et al. Factors influencing the outcome of closed tibial fractures treated with functional bracing. Clin Orthop Relat Res. 1995; 315: 8-24.
29. Oni OO, Hui A, Gregg PJ. The healing of closed tibial shaft fractures. The natural history of union with closed treatment. J Bone Joint Surg Br. 1988; 70: 787-90.
30. Iwakura T, Miwa M, Sakai Y, et al. Human hypertrophic nonunion tissue contains mesenchymal progenitor cells with multilineage capacity in vitro. J Orthop Res. 2009; 27: 208-15.
31. Pneumaticos SG, Panteli M, Triantafyllopoulos GK, et al. Management and outcome of diaphyseal aseptic non-unions of the lower limb: a systematic review. Surgeon. 2014; 12 (3): 166-75.
32. Heppenstall RB, Brighton CT, Esterhai JL. Synovial pseudarthrosis: a clinical, roentgenographic-scintigraphic, and pathologic study. J Trauma. 1987; 27: 463-70.
33. Zeckey C, Hildebrand F, Glaubitz LM, et al. Are polymorphisms of molecules involved in bone healing correlated to aseptic femoral and tibial shaft non-unions? J Orthop Res. 2011; 29: 1724-31.
34. Einhorn TA. Enhancement of fracture healing. Instr Course Lect. 1996; 45: 401-16.
35. Kwong FN, Hoyland JA, Freemont AJ, et al. Altered relative expression of BMPs and BMP inhibitors in cartilaginous areas of human fractures progressing towards nonunion. J Orthop Res. 2009; 27: 752-7.
36. Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009; 339: b2535.
37. Palmer MP, Altman DT, Altman GT, et al. Can we trust intraoperative culture results in nonunions? J Orthop Trauma. 2014; 28: 384-90.
38. Gille J, Wallstabe S, Schulz AP, et al. Is non-union of tibial shaft fractures due to nonculturable bacterial pathogens? A clinical investigation using PCR and culture techniques. J Orthop Surg Res. 2012; 7: 20.
39. Fajardo M, Liu CJ, Egol K. Levels of expression for BMP-7 and several BMP antagonists may play an integral role in a fracture nonunion: a pilot study. Clin Orthop Relat Res. 2009; 467: 3071-8.
40. Bajada S, Marshall MJ, Wright KT, et al. Decreased osteogenesis, increased cell senescence and elevated Dickkopf-1 secretion in human fracture non union stromal cells. Bone. 2009; 45: 726-35.
41. Qu G, von Schroeder HP. The osteogenic potential of pseudoarthrosis tissue and bone from human scaphoid non-unions. J Hand Surg Eur Vol. 2008; 33: 449-56.
42. Hofmann A, Ritz U, Hessmann MH, et al. Cell viability, osteoblast differentiation, and gene expression are altered in human osteoblasts from hypertrophic fracture non-unions. Bone. 2008; 42: 894-906.
43. Bajada S, Harrison PE, Ashton BA, et al. Successful treatment of refractory tibial nonunion using calcium sulphate and bone marrow stromal cell implantation. J Bone Joint Surg Br. 2007; 89: 1382-6.
44. Reed AA, Joyner CJ, Brownlow HC, et al. Human atrophic fracture non-unions are not avascular. J Orthop Res. 2002; 20: 593-9.
45. Kloen P, Doty SB, Gordon E, et al. Expression and activation of the BMP-signaling components in human fracture nonunions. J Bone Joint Surg Am. 2002; 84-A: 1909-18.
46. Guerkov HH, Lohmann CH, Liu Y, et al. Pulsed electromagnetic fields increase growth factor release by nonunion cells. Clin Orthop Relat Res. 2001; 384: 265-79.
47. Lawton DM, Andrew JG, Marsh DR, et al. Mature osteoblasts in human non-union fractures express collagen type III. Mol Pathol. 1997; 50: 194-7.
48. Santavirta S, Konttinen YT, Nordstrom D, et al. Immunologic studies of nonunited fractures. Acta Orthop Scand. 1992; 63: 579-86.
49. Boyan BD, Schwartz Z, Swain LD, et al. Initial effects of partially purified bone morphogenetic protein on the expression of glycosaminoglycan, collagen, and alkaline phosphatase in nonunion cell cultures. Clin Orthop Relat Res. 1992; 278: 286-304.
50. Quacci D, Dell'Orbo C, Salvi M, et al. Ultrastructural aspects of human nonunion. Histol Histopathol. 1991; 6: 87-93.
51. Milgram JW. Nonunion and pseudarthrosis of fracture healing. A histopathologic study of 95 human specimens. Clin Orthop Relat Res. 1991; 268: 203-13.
52. Kilian O, Dahse R, Alt V, et al. Expression of EDA+ and EDB+ fibronectin splice variants in bone. Bone. 2004; 35: 1334-45.
53. Urist MR, Mazet R Jr, McLean FC. The pathogenesis and treatment of delayed union and non-union; a survey of eighty-five ununited fractures of the shaft of the tibia and one hundred control cases with similar injuries. J Bone Joint Surg Am. 1954; 36-A: 931-80; passim.
54. Dimitriou R, Carr IM, West RM, et al. Genetic predisposition to fracture non-union: a case control study of a preliminary single nucleotide polymorphisms analysis of the BMP pathway. BMC Musculoskelet Disord. 2011; 12: 44.
55. Xiong DH, Liu XG, Guo YF, et al. Genome-wide association and follow-up replication studies identified ADAMTS18 and TGFBR3 as bone mass candidate genes in different ethnic groups. Am J Hum Genet. 2009; 84: 388-98.
56. Dimitriou R, Kanakaris N, Soucacos PN, et al. Genetic predisposition to non-union: evidence today. Injury. 2013; 44: S50-3.
57. Fernandez-Bances I, Perez-Basterrechea M, Perez-Lopez S, et al. Repair of long-bone pseudoarthrosis with autologous bone marrow mononuclear cells combined with allogenic bone graft. Cytotherapy. 2013; 15: 571-7.
58. Paley D, Catagni MA, Argnani F, et al. Ilizarov treatment of tibial nonunions with bone loss. Clin Orthop Relat Res. 1989; 241: 146-65.
59. Panousis K, Grigoris P, Butcher I, et al. Poor predictive value of broad-range PCR for the detection of arthroplasty infection in 92 cases. Acta Orthop. 2005; 76: 341-6.
60. Behrens A, van Deursen JM, Rudolph KL, et al. Impact of genomic damage and ageing on stem cell function. Nat Cell Biol. 2014; 16: 201-7.
61. Man J, Shelton RM, Cooper PR, et al. Low intensity ultrasound stimulates osteoblast migration at different frequencies. J Bone Miner Metab. 2012; 30: 602-7.
62. Watanabe Y, Arai Y, Takenaka N, et al. Three key factors affecting treatment results of low-intensity pulsed ultrasound for delayed unions and nonunions: instability, gap size, and atrophic nonunion. J Orthop Sci. 2013; 18: 803-10.
63. Chen Y, Whetstone HC, Lin AC, et al. Beta-catenin signaling plays a disparate role in different phases of fracture repair: implications for therapy to improve bone healing. PLoS Med. 2007; 4: e249.
64. Pountos I, Georgouli T, Kontakis G, et al. Efficacy of minimally invasive techniques for enhancement of fracture healing: evidence today. Int Orthop. 2010; 34: 3-12.