Skip to main content
Top
Published in: BMC Musculoskeletal Disorders 1/2019

Open Access 01-12-2019 | Scoliosis | Research article

Differential proteome analysis in adolescent idiopathic scoliosis patients with thoracolumbar/lumbar curvatures

Published in: BMC Musculoskeletal Disorders | Issue 1/2019

Login to get access

Abstract

Background

Although the pathogenesis of adolescent idiopathic scoliosis (AIS) remains unclear, there are little evidences of the pathogenesis in patients with thoracolumbar/lumbar AIS. The purpose of this study was to identify proteins or proteomes that may be causally related to the pathogenesis of AIS with structured thoracolumbar/lumbar curvature using two-dimensional fluorescence difference gel electrophoresis (2D-DIGE).

Methods

A total of 20 control volunteers and 61 AIS in patients with thoracolumbar/lumbar curvature were included. First, the plasma samples of each five AIS with pure thoracolumbar/lumbar curvature and control samples were subjected to 2D-DIGE analysis. Protein spots that were expressed differently by the AIS and control groups were selected and identified by nanoscale liquid chromatography–tandem mass spectrometry (nanoLC-MS/MS) analysis. To characterize the differently-expressed proteins in AIS patients, we performed functional pathway analysis using the Protein ANalysis THrough Evolutionary Relationships (PANTHER) system. Additionally, the proteins were compared between control and AIS using western blotting. Lastly, prospectively collected 15 control and 41 AIS with thoracolumbar/lumbar curvature samples were compared to the differentially expressed proteins.

Results

A total of 3862 ± 137 spots were detected, of which 11 spots met the criteria when compared with controls. Nine proteins were identified by nanoLC-MS/MS. Functional analysis showed the association of the proteins in AIS patients with blood coagulation using the PANTHER system. Of the proteins, vitamin D binding protein (DBP) significantly correlated with Cobb angle in thoracolumbar/lumbar curvatures. DBP expression of the prospectively collected AIS samples were significantly higher than those of controls (P < 0.05).

Conclusions

This study suggests that DBP and several coagulation-related proteins may play a role in the pathogenesis of AIS. DBP appears to be a marker of severity of AIS with thoracolumbar/lumbar curvature.
Literature
1.
go back to reference Kane WJ. Scoliosis prevalence: a call for a statement of terms. Clin Orthop Relat Res. 1997;126:43–6. Kane WJ. Scoliosis prevalence: a call for a statement of terms. Clin Orthop Relat Res. 1997;126:43–6.
2.
go back to reference Weinstein SL. Natural history. Spine (Phila Pa 1976). 1999;24(24):2592–600.CrossRef Weinstein SL. Natural history. Spine (Phila Pa 1976). 1999;24(24):2592–600.CrossRef
3.
go back to reference Johnston CE, Richards BS, Sucato DJ, Bridwell KH, Lenke LG, Erickson M, Spinal Deformity Study Group. Correlation of preoperative deformity magnitude and pulmonary function tests in adolescent idiopathic scoliosis. Spine (Phila Pa 1976). 2011;36(14):1096–102.CrossRef Johnston CE, Richards BS, Sucato DJ, Bridwell KH, Lenke LG, Erickson M, Spinal Deformity Study Group. Correlation of preoperative deformity magnitude and pulmonary function tests in adolescent idiopathic scoliosis. Spine (Phila Pa 1976). 2011;36(14):1096–102.CrossRef
4.
go back to reference Theroux J, Le May S, Hebert JJ, Labelle H. Back pain prevalence is associated with curve-type and severity in adolescents with idiopathic scoliosis: a cross-sectional study. Spine (Phila Pa 1976). 2017;42(15):E914–9.CrossRef Theroux J, Le May S, Hebert JJ, Labelle H. Back pain prevalence is associated with curve-type and severity in adolescents with idiopathic scoliosis: a cross-sectional study. Spine (Phila Pa 1976). 2017;42(15):E914–9.CrossRef
5.
go back to reference Lonstein JE. Scoliosis: surgical versus nonsurgical treatment. Clin Orthop Relat Res. 2006;443:248–59.CrossRef Lonstein JE. Scoliosis: surgical versus nonsurgical treatment. Clin Orthop Relat Res. 2006;443:248–59.CrossRef
6.
go back to reference Coe JD, Arlet V, Donaldson W, Berven S, Hanson DS, Mudiyam R, Perra JH, Shaffrey CI. Complications in spinal fusion for adolescent idiopathic scoliosis in the new millennium. A report of the Scoliosis Research Society morbidity and mortality committee. Spine (Phila Pa 1976). 2006;31(3):345–9.CrossRef Coe JD, Arlet V, Donaldson W, Berven S, Hanson DS, Mudiyam R, Perra JH, Shaffrey CI. Complications in spinal fusion for adolescent idiopathic scoliosis in the new millennium. A report of the Scoliosis Research Society morbidity and mortality committee. Spine (Phila Pa 1976). 2006;31(3):345–9.CrossRef
7.
go back to reference Takahashi Y, Kou I, Takahashi A, Johnson TA, Kono K, Kawakami N, Uno K, Ito M, Minami S, Yanagida H, Taneichi H, Tsuji T, Suzuki T, Sudo H, Kotani T, Watanabe K, Chiba K, Hosono N, Kamatani N, Tsunoda T, Toyama Y, Kubo M, Matsumoto M, Ikegawa S. A genome-wide association study identifies common variants near LBX1 associated with adolescent idiopathic scoliosis. Nat Genet. 2011;43(12):1237–40.CrossRef Takahashi Y, Kou I, Takahashi A, Johnson TA, Kono K, Kawakami N, Uno K, Ito M, Minami S, Yanagida H, Taneichi H, Tsuji T, Suzuki T, Sudo H, Kotani T, Watanabe K, Chiba K, Hosono N, Kamatani N, Tsunoda T, Toyama Y, Kubo M, Matsumoto M, Ikegawa S. A genome-wide association study identifies common variants near LBX1 associated with adolescent idiopathic scoliosis. Nat Genet. 2011;43(12):1237–40.CrossRef
8.
go back to reference Kou I, Takahashi Y, Johnson TA, Takahashi A, Guo L, Dai J, Qiu X, Sharma S, Takimoto A, Ogura Y, Jiang H, Yan H, Kono K, Kawakami N, Uno K, Ito M, Minami S, Yanagida H, Taneichi H, Hosono N, Tsuji T, Suzuki T, Sudo H, Kotani T, Yonezawa I, Londono D, Gordon D, Herring JA, Watanabe K, Chiba K, Kamatani N, Jiang Q, Hiraki Y, Kubo M, Toyama Y, Tsunoda T, Wise CA, Qiu Y, Shukunami C, Matsumoto M, Ikegawa S. Genetic variants in GPR126 are associated with adolescent idiopathic scoliosis. Nat Genet. 2013;45(6):676–9.CrossRef Kou I, Takahashi Y, Johnson TA, Takahashi A, Guo L, Dai J, Qiu X, Sharma S, Takimoto A, Ogura Y, Jiang H, Yan H, Kono K, Kawakami N, Uno K, Ito M, Minami S, Yanagida H, Taneichi H, Hosono N, Tsuji T, Suzuki T, Sudo H, Kotani T, Yonezawa I, Londono D, Gordon D, Herring JA, Watanabe K, Chiba K, Kamatani N, Jiang Q, Hiraki Y, Kubo M, Toyama Y, Tsunoda T, Wise CA, Qiu Y, Shukunami C, Matsumoto M, Ikegawa S. Genetic variants in GPR126 are associated with adolescent idiopathic scoliosis. Nat Genet. 2013;45(6):676–9.CrossRef
9.
go back to reference Schlösser TP, van der Heijden GJ, Versteeg AL, Castelein RM. How “idiopathic” is adolescent idiopathic scoliosis? A systematic review on associated abnormalities. PLoS One. 2014;9(5):e97461.CrossRef Schlösser TP, van der Heijden GJ, Versteeg AL, Castelein RM. How “idiopathic” is adolescent idiopathic scoliosis? A systematic review on associated abnormalities. PLoS One. 2014;9(5):e97461.CrossRef
10.
go back to reference Zhuang Q, Li J, Wu Z, Zhang J, Sun W, Li T, Yan Y, Jiang Y, Zhao RC, Qiu G. Differential proteome analysis of bone marrow mesenchymal stem cells from adolescent idiopathic scoliosis patients. PLoS One. 2011;6(4):e18834.CrossRef Zhuang Q, Li J, Wu Z, Zhang J, Sun W, Li T, Yan Y, Jiang Y, Zhao RC, Qiu G. Differential proteome analysis of bone marrow mesenchymal stem cells from adolescent idiopathic scoliosis patients. PLoS One. 2011;6(4):e18834.CrossRef
11.
go back to reference Ishida K, Aota Y, Mitsugi N, Kono M, Higashi T, Kawai T, Yamada K, Niimura T, Kaneko K, Tanabe H, Ito Y, Katsuhata T, Saito T. Relationship between bone density and bone metabolism in adolescent idiopathic scoliosis. Scoliosis. 2015;10(19):9.CrossRef Ishida K, Aota Y, Mitsugi N, Kono M, Higashi T, Kawai T, Yamada K, Niimura T, Kaneko K, Tanabe H, Ito Y, Katsuhata T, Saito T. Relationship between bone density and bone metabolism in adolescent idiopathic scoliosis. Scoliosis. 2015;10(19):9.CrossRef
12.
go back to reference Wang WJ, Sun C, Liu Z, Sun X, Zhu F, Zhu ZZ, Qiu Y. Transcription factor Runx2 in the low bone mineral density of girls with adolescent idiopathic scoliosis. Orthop Surg. 2014;6(1):8–14.CrossRef Wang WJ, Sun C, Liu Z, Sun X, Zhu F, Zhu ZZ, Qiu Y. Transcription factor Runx2 in the low bone mineral density of girls with adolescent idiopathic scoliosis. Orthop Surg. 2014;6(1):8–14.CrossRef
13.
go back to reference Lenke LG, Betz RR, Harms J, Bridwell KH, Clements DH, Lowe TG, Blanke K. Adolescent idiopathic scoliosis: a new classification to determine extent of spinal arthrodesis. J Bone Joint Surg Am. 2001;83-A(8):1169–81.CrossRef Lenke LG, Betz RR, Harms J, Bridwell KH, Clements DH, Lowe TG, Blanke K. Adolescent idiopathic scoliosis: a new classification to determine extent of spinal arthrodesis. J Bone Joint Surg Am. 2001;83-A(8):1169–81.CrossRef
14.
go back to reference Burwell RG. Aetiology of idiopathic scoliosis: current concepts. Pediatr Rehabil. 2003;6(3–4):137–70.CrossRef Burwell RG. Aetiology of idiopathic scoliosis: current concepts. Pediatr Rehabil. 2003;6(3–4):137–70.CrossRef
15.
go back to reference Burwell RG, Clark EM, Dangerfield PH, Moulton A. Adolescent idiopathic scoliosis (AIS): a multifactorial cascade concept for pathogenesis and embryonic origin. Scoliosis Spinal Disord. 2016;11(30):8.CrossRef Burwell RG, Clark EM, Dangerfield PH, Moulton A. Adolescent idiopathic scoliosis (AIS): a multifactorial cascade concept for pathogenesis and embryonic origin. Scoliosis Spinal Disord. 2016;11(30):8.CrossRef
16.
go back to reference Mi H, Muruganujan A, Casagrande JT, Thomas PD. Large-scale gene function analysis with the PANTHER classification system. Nat Protoc. 2013;8(8):1551–66.CrossRef Mi H, Muruganujan A, Casagrande JT, Thomas PD. Large-scale gene function analysis with the PANTHER classification system. Nat Protoc. 2013;8(8):1551–66.CrossRef
17.
go back to reference Ryan KM, O'Brien K, Regan I, O'Byrne JM, Moore D, Kelly PM, Noel J, Butler J, Nolan B, Kiely PJ. The prevalence of abnormal preoperative coagulation tests in pediatric patients undergoing spinal surgery for scoliosis. Spine J. 2015;15(6):1217–22.CrossRef Ryan KM, O'Brien K, Regan I, O'Byrne JM, Moore D, Kelly PM, Noel J, Butler J, Nolan B, Kiely PJ. The prevalence of abnormal preoperative coagulation tests in pediatric patients undergoing spinal surgery for scoliosis. Spine J. 2015;15(6):1217–22.CrossRef
18.
go back to reference Ho WK, Baccala M, Thom J, Eikelboom JW. High prevalence of abnormal preoperative coagulation tests in patients with adolescent idiopathic scoliosis. J Thromb Haemost. 2005;3(5):1094–5.CrossRef Ho WK, Baccala M, Thom J, Eikelboom JW. High prevalence of abnormal preoperative coagulation tests in patients with adolescent idiopathic scoliosis. J Thromb Haemost. 2005;3(5):1094–5.CrossRef
19.
go back to reference Bosch P, Kenkre TS, Londino JA, Cassara A, Yang C, Waters JH. Coagulation profile of patients with adolescent idiopathic scoliosis undergoing posterior spinal fusion. J Bone Joint Surg Am. 2016;98(20):e88.CrossRef Bosch P, Kenkre TS, Londino JA, Cassara A, Yang C, Waters JH. Coagulation profile of patients with adolescent idiopathic scoliosis undergoing posterior spinal fusion. J Bone Joint Surg Am. 2016;98(20):e88.CrossRef
20.
go back to reference Christiansen M, Jørgensen CS, Laursen I, Hirschberg D, Højrup P, Houen G. Protein chemical characterization of Gc globulin (vitamin D-binding protein) isoforms; Gc-1f, Gc-1s and Gc-2. Biochim Biophys Acta. 2007;1774(4):481–92.CrossRef Christiansen M, Jørgensen CS, Laursen I, Hirschberg D, Højrup P, Houen G. Protein chemical characterization of Gc globulin (vitamin D-binding protein) isoforms; Gc-1f, Gc-1s and Gc-2. Biochim Biophys Acta. 2007;1774(4):481–92.CrossRef
21.
go back to reference Al-oanzi ZH, Tuck SP, Mastana SS, Summers GD, Cook DB, Francis RM, Datta HK. Vitamin D-binding protein gene microsatellite polymorphism influences BMD and risk of fractures in men. Osteoporos Int. 2008;19(7):951–60.CrossRef Al-oanzi ZH, Tuck SP, Mastana SS, Summers GD, Cook DB, Francis RM, Datta HK. Vitamin D-binding protein gene microsatellite polymorphism influences BMD and risk of fractures in men. Osteoporos Int. 2008;19(7):951–60.CrossRef
22.
go back to reference Wang Y, Cui ZQ, Luo TB, Liu L. Correlations of VDR and VDBP genetic polymorphisms with susceptibility to adolescent idiopathic scoliosis and efficacy of brace treatment. Genomics. 2016;108(5–6):194–200.CrossRef Wang Y, Cui ZQ, Luo TB, Liu L. Correlations of VDR and VDBP genetic polymorphisms with susceptibility to adolescent idiopathic scoliosis and efficacy of brace treatment. Genomics. 2016;108(5–6):194–200.CrossRef
23.
go back to reference Goździalska A, Jaśkiewicz J, Knapik-Czajka M, Drąg J, Gawlik M, Cieśla M, Kulis A, Zarzycki D, Lipik E. Association of calcium and phosphate balance, vitamin D, PTH, and calcitonin in patients with adolescent idiopathic scoliosis. Spine (Phila Pa 1976). 2016;41(8):693–7.CrossRef Goździalska A, Jaśkiewicz J, Knapik-Czajka M, Drąg J, Gawlik M, Cieśla M, Kulis A, Zarzycki D, Lipik E. Association of calcium and phosphate balance, vitamin D, PTH, and calcitonin in patients with adolescent idiopathic scoliosis. Spine (Phila Pa 1976). 2016;41(8):693–7.CrossRef
24.
go back to reference Balioglu MB, Aydin C, Kargin D, Albayrak A, Atici Y, Tas SK, Kaygusuz MA. Vitamin-D measurement in patients with adolescent idiopathic scoliosis. J Pediatr Orthop B. 2017;26(1):48–52.CrossRef Balioglu MB, Aydin C, Kargin D, Albayrak A, Atici Y, Tas SK, Kaygusuz MA. Vitamin-D measurement in patients with adolescent idiopathic scoliosis. J Pediatr Orthop B. 2017;26(1):48–52.CrossRef
25.
go back to reference Bikle DD, Gee E. Free, and not total, 1,25-dihydroxyvitamin D regulates 25-hydroxyvitamin D metabolism by keratinocytes. Endocrinology. 1989;124(2):649–54.CrossRef Bikle DD, Gee E. Free, and not total, 1,25-dihydroxyvitamin D regulates 25-hydroxyvitamin D metabolism by keratinocytes. Endocrinology. 1989;124(2):649–54.CrossRef
26.
go back to reference Peris P, Filella X, Monegal A, Guañabens N, Foj L, Bonet M, Boquet D, Casado E, Cerdá D, Erra A, Gómez-Vaquero C, Martínez S, Montalá N, Pittarch C, Kanterewicz E, Sala M, Suris X, Carrasco JL, LabOscat Study Group. Comparison of total, free and bioavailable 25-OH vitamin D determinations to evaluate its biological activity in healthy adults: the LabOscat study. Osteoporos Int. 2017;28(8):2457–64.CrossRef Peris P, Filella X, Monegal A, Guañabens N, Foj L, Bonet M, Boquet D, Casado E, Cerdá D, Erra A, Gómez-Vaquero C, Martínez S, Montalá N, Pittarch C, Kanterewicz E, Sala M, Suris X, Carrasco JL, LabOscat Study Group. Comparison of total, free and bioavailable 25-OH vitamin D determinations to evaluate its biological activity in healthy adults: the LabOscat study. Osteoporos Int. 2017;28(8):2457–64.CrossRef
27.
go back to reference Nagasawa H, Uto Y, Sasaki H, Okamura N, Murakami A, Kubo S, Kirk KL, Hori H. Gc protein (vitamin D-binding protein): Gc genotyping and GcMAF precursor activity. Anticancer Res. 2005;25(6A):3689–95.PubMed Nagasawa H, Uto Y, Sasaki H, Okamura N, Murakami A, Kubo S, Kirk KL, Hori H. Gc protein (vitamin D-binding protein): Gc genotyping and GcMAF precursor activity. Anticancer Res. 2005;25(6A):3689–95.PubMed
28.
go back to reference Pollard SL, Lima JJ, Mougey E, Romero K, Tarazona-Meza C, Tomaino K, Guzmán GM, Hansel NN, Checkley W, Genetics of Asthma Susceptibility to Pollution (GASP) Study Investigators. Free 25(OH)D concentrations are associated with atopy and lung function in children with asthma. Ann Allergy Asthma Immunol. 2017;119(1):37–41.CrossRef Pollard SL, Lima JJ, Mougey E, Romero K, Tarazona-Meza C, Tomaino K, Guzmán GM, Hansel NN, Checkley W, Genetics of Asthma Susceptibility to Pollution (GASP) Study Investigators. Free 25(OH)D concentrations are associated with atopy and lung function in children with asthma. Ann Allergy Asthma Immunol. 2017;119(1):37–41.CrossRef
29.
go back to reference Pelczyńska M, Grzelak T, Sperling M, Bogdański P, Pupek-Musialik D, Czyżewska K. Impact of 25-hydroxyvitamin D, free and bioavailable fractions of vitamin D, and vitamin D binding protein levels on metabolic syndrome components. Arch Med Sci. 2017;13(4):745–52.CrossRef Pelczyńska M, Grzelak T, Sperling M, Bogdański P, Pupek-Musialik D, Czyżewska K. Impact of 25-hydroxyvitamin D, free and bioavailable fractions of vitamin D, and vitamin D binding protein levels on metabolic syndrome components. Arch Med Sci. 2017;13(4):745–52.CrossRef
30.
go back to reference Lonner BS, Toombs CS, Husain QM, Sponseller P, Shufflebarger H, Shah SA, Samdani AF, Betz RR, Cahill PJ, Yaszay B, Newton PO. Body mass index in adolescent spinal deformity: comparison of Scheuermann's kyphosis, adolescent idiopathic scoliosis, and Normal controls. Spine Deform. 2015;3(4):318–26.CrossRef Lonner BS, Toombs CS, Husain QM, Sponseller P, Shufflebarger H, Shah SA, Samdani AF, Betz RR, Cahill PJ, Yaszay B, Newton PO. Body mass index in adolescent spinal deformity: comparison of Scheuermann's kyphosis, adolescent idiopathic scoliosis, and Normal controls. Spine Deform. 2015;3(4):318–26.CrossRef
Metadata
Title
Differential proteome analysis in adolescent idiopathic scoliosis patients with thoracolumbar/lumbar curvatures
Publication date
01-12-2019
Published in
BMC Musculoskeletal Disorders / Issue 1/2019
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/s12891-019-2640-y

Other articles of this Issue 1/2019

BMC Musculoskeletal Disorders 1/2019 Go to the issue