Proteomic analysis of plasma profiles in children with recurrent bone fractures
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The aim of the study is proteomic analysis of the plasma profile in children with recurrent bone fractures. The study involved 16 children: 6 patients with recurrent low-energy fractures and normal bone mass and 10 with osteogenesis imperfecta. In the analysis of the protein profile, the two-dimensional protein electrophoresis was used (Ettan DALT II, Amersham Bioscience). The images of protein gels were compared with controls. The protein spots with changed expression were cut from the gel and the amino acid sequence was analyzed with the mass spectrometry method (Q-Tof PremierTM API MASS SPECTROMETR, Waters) for protein identification. The most prevalent protein with changed expression, with respect to controls, was haptoglobin observed in 6 patients with a severe form of osteogenesis imperfecta. Increased haptoglobin concentration in these patients was confirmed by the ELISA method. Peptides corresponding to alpha-1 acid glycoprotein and serum amyloid P-component, apolipoprotein A-I, and transthyretin were detected in one, two and three children, respectively. Conclusions: 1) The results show increased haptoglobin which may be suggestive of an inflammatory component taking part in the course of osteogenesis imperfecta. 2) Further studies to explain the possible relationship of this protein with increased bone fragility are necessary.
- Campos MS, Barrionuevo M, Alferez MJ, Gomez-Ayala AE, Rodriguez-Mata MC, Lopez O (1998) Interactions among iron, calcium, phosphorus and magnesium in the nutritionally iron-deficient rat. Exp Physiol 83: 771-781.
- Carstanjen D, Regenfus M, Müller C, Salama A (2001) Interleukin-6 is a major effector molecule of short-term G-CSF treatment inducing bone metabolism and an acute-phase response. Exp Hematol 29: 812-821.
- Clark EM, Tobias JH, Ness AR (2006) Association between bone density and fractures in children: a systematic review and meta-analysis. Pediatrics 117: e291-297.
- Cundy T, Horne A, Bolland M, Gamble G, Davidson J (2007) Bone formation markers in adults with mild oseogenesis imperfecta. Clin Chem 53: 1109-1114.
- D'Amelio P, Cristofaro MA, Tamone C, Morra E, Di Bella S, Isaia G, Grimaldi A, Gennero L, Gariboldi A, Ponzetto A, Pescarmona GP, Isaia GC (2008) Role of iron metabolism and oxidative damage in postmenopausal bone loss. Bone 43: 1010-1015.
- D'Amelio P, Di Bella S, Tamone C, Ravazzoli MG, Cristofaro MA, Di Stefano M, Isaia G (2008) HDL cholesterol and bone mineral density in normal-weight postmenopausal women: is there any possible association? Panminerva Med 50: 89-96.
- de Ceuninck F (2008) The application of proteomics to articular cartilage: a new hope for the treatment of osteoarthritis. Joint Bone Spine 75: 376-378.
- Delanghe J, Langlois M, Duprez D, De Buyzere M, Clement D (1999) Haptoglobin polymorphism and peripheral arterial occlusive disease. Atherosclerosis 145: 287-292.
- Fonseca JE, Santos MJ, Canhão H, Choy E (2009) Interleukin-6 as a key player in systemic inflammation and joint destruction. Autoimmun Rev 8: 538-542.
- Forlino A, Tani C, Rossi A, Lupi A, Campari E, Gualeni B, Bianchi L, Armini A, Cetta G, Bini L, Marini JC (2007) Differential expression of both extracellular and intracellular proteins is involved in the lethal or nonlethal phenotypic variation of BrtlIV, a murine model for osteogenesis imperfecta. Proteomics 7: 1877-1891.
- Khosla S, Melton LJ 3rd, Dekutoski MB, Achenbach SJ, Oberg AL, Riggs BL (2003) Incidence of childhood distal forearm fractures over 30 years: a population-based study. JAMA 290: 1479-1485.
- Lerner UH, Fröhlander N (1992) Haptoglobin-stimulated bone resorption in neonatal mouse calvarial bones in vitro. Arthritis Rheum 35: 587-591.
- Manias K, McCabe D, Bishop N (2006) Fractures and recurrent fractures in children; varying effects of environmental factors as well as bone size and mass. Bone 39: 652-657.
- Mayer-Kuckuk P, Boskey AL (2006) Molecular imaging promotes progress in orthopedic research. Bone 39: 965-977.
- Mundy GR (2007) Osteoporosis and inflammation. Nutr Rev 65: S147-151.
- Pernow Y, Hauge EM, Linder K, Dahl E, Sääf M (2009) Bone histomorphometry in male idiopathic osteoporosis. Calcif Tissue Int 84: 430-438.
- Rusińska A, Chlebna-Sokół D (2005) Evaluation of interleukin-1 and -6 in the etiopathogenesis of idiopathic osteoporosis and osteopenia in children. Arch Immunol Ther Exp (Warsz) 53: 257-265.
- Shevchenko A, Wilm M, Vorm O, Mann M (1996) Mass spectrometric sequencing of proteins silver-stained polyacrylamide gels. Anal Chem 68: 850-858.
- Van Vlierberghe H, Langlois M, Delanghe J (2004) Haptoglobin polymorphisms and iron homeostasis in health and in disease. Clin Chim Acta 345: 35-42.
- Zhang H, Recker R, Lee WN, Xiao GG (2010) Proteomics in bone research. Expert Rev Proteomics 7: 103-111.
- Zheng X, Wu SL, Hincapie M, Hancock WS (2009) Study of the human plasma proteome of rheumatoid arthritis. J Chromatogr A 1216: 3538-3545.
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