Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Musculoskeletal Disorders
Published in: BMC Musculoskeletal Disorders 1/2015

Open Access 01-12-2015 | Research article

Comparative study of serum proteomes in Legg-Calve-Perthes disease

Authors: Ruiyu Liu, Lihong Fan, Longbin Yin, Kunzheng Wang, Wusheng Miao, Qichun Song, Xiaoqian Dang, Hang Gao, Chuanyi Bai

Published in: BMC Musculoskeletal Disorders | Issue 1/2015

Login to get access

Abstract

Background

Legg-Calve-Perthes Disease (LCPD) is an idiopathic osteonecrosis of the developing femoral head complicated by pain and disability of the hip joint. To date, the pathological mechanisms of LCPD are not well-known. This study screened the changes in serum protein expression in patients with LCPD.

Methods

Age- and sex-matched serum samples from 10 control subjects and 10 patients with LCPD were compared using the isobaric tags for relative and absolute quantification (iTRAQ) technique. Gene ontology analyses, KEGG pathway and functional network analyses were performed. Proteins of interest with large differences in expression, S100-A8, alpha-1-acid glycoprotein 1, haptoglobin and apolipoprotein E, were compared by western blotting.

Results

The disease/control ratios showed 26 proteins were significantly differentially expressed (all p < 0.05). Including higher abundances of complement factor H (1.44), complement C4-B (1.45), isocitrate dehydrogenase [NAD] subunit alpha (2.7) alpha-1-acid glycoprotein 1 (1.87), heptoglobin (1.53) and Ig lambda-2 chain C regions (1.46), and lower levels of apolipoprotein E (0.50), apolipoprotein F (0.60), apolipoprotein C-III (0.69), S100-A8 (0.73), S100-A9 (0.75) and prothrombin (0.77) in LCPD than in controls. The alpha-1-acid glycoprotein 1 and haptoglobin increases, and apolipoprotein E and S100-A8 decreases were confirmed by western blot. KEGG pathway analysis revealed these proteins were related to the complement and coagulation cascades, Staphylococcus aureus infection, PPAR signaling, fat digestion and absorption, and vitamin digestion and absorption. Functional network analysis suggested that the proteins were involved in lipid regulation.

Conclusions

The complement and coagulation cascades, and abnormal lipid metabolism may be involved in the pathogenesis of LCPD.
Literature
1.
Perry DC, Machin DM, Pope D, Bruce CE, Dangerfield P, Platt MJ, et al. Racial and geographic factors in the incidence of Legg-Calvé-Perthes’ disease: a systematic review. Am J Epidemiol. 2012;175(3):159–66.CrossRefPubMed
2.
Guille JT, Lipton GE, Szöke G, Bowen JR, Harcke HT, Glutting JJ. Legg-Calvé-Perthes disease in girls. A comparison of the results with those seen in boys. J Bone Joint Surg Am. 1998;80(9):1256–63.PubMed
3.
4.
Aksoy MC, Aksoy DY, Haznedaroglu IC, Sayinalp N, Kirazli S, Alpaslan M. Thrombomodulin and GFC levels in Legg-Calve-Perthes disease. Hematology. 2008;13(6):324–8.CrossRefPubMed
5.
Vosmaer A, Pereira RR, Koenderman JS, Rosendaal FR, Cannegieter SC. Coagulation abnormalities in Legg-Calvé-Perthes disease. J Bone Joint Surg Am. 2010;92(1):121–8.CrossRefPubMed
6.
Balasa VV, Gruppo RA, Glueck CJ, Wang P, Roy DR, Wall EJ, et al. Legg-Calve-Perthes disease and thrombophilia. J Bone Joint Surg Am. 2004;86-A(12):2642–7.PubMed
7.
Atsumi T, Yamano K, Muraki M, Yoshihara S, Kajihara T. The blood supply of the lateral epiphyseal arteries in Perthes’ disease. J Bone Joint Surg Br. 2000;82(3):392–8.CrossRefPubMed
8.
Gaĭko GV, Goncharova LD, Zolotukhin SE, Donchenko LI. [Mechanism of early metabolism disorders and immunological reactivity in children with Perthes disease]. Lik Sprava. 2001;1:56–61. Russian.PubMed
9.
Lee JH, Zhou L, Kwon KS, Lee D, Park BH, Kim JR. Role of leptin in legg-calvé-perthes disease. J Orthop Res. 2013;31(10):1605–10.CrossRefPubMed
10.
Perry DC, Green DJ, Bruce CE, Pope D, Dangerfield P, Platt MJ, et al. Abnormalities of vascular structure and function in children with Perthes disease. Pediatrics. 2012;130(1):e126–31.CrossRefPubMed
11.
Kamiya N, Shafer S, Oxendine I, Mortlock DP, Chandler RL, Oxburgh L, et al. Acute BMP2 upregulation following induction of ischemic osteonecrosis in immature femoral head. Bone. 2013;53(1):239–47.CrossRefPubMed
12.
Kim HK, Bian H, Randall T, Garces A, Gerstenfeld LC, Einhorn TA. Increased VEGF expression in the epiphyseal cartilage after ischemic necrosis of the capital femoral epiphysis. J Bone Miner Res. 2004;19(12):2041–8.CrossRefPubMed
13.
Hofstaetter JG, Roschger P, Klaushofer K, Kim HK. Increased matrix mineralization in the immature femoral head following ischemic osteonecrosis. Bone. 2010;46(2):379–85.CrossRefPubMed
14.
Zhang H, Zhang L, Wang J, Ma Y, Zhang J, Mo F, et al. Proteomic analysis of bone tissues of patients with osteonecrosis of the femoral head. OMICS. 2009;13(6):453–66.CrossRefPubMed
15.
Wu RW, Wang FS, Ko JY, Wang CJ, Wu SL. Comparative serum proteome expression of osteonecrosis of the femoral head in adults. Bone. 2008;43(3):561–6.CrossRefPubMed
16.
Wiśniewski JR, Zougman A, Mann M. Combination of FASP and StageTip-based fractionation allows in-depth analysis of the hippocampal membrane proteome. J Proteome Res. 2009;8(12):5674–8.CrossRefPubMed
17.
Carbon S, Ireland A, Mungall CJ, Shu S, Marshall B, Lewis S, et al. Web Presence Working Group. AmiGO: online access to ontology and annotation data. Bioinformatics. 2009;25(2):288–9.CrossRefPubMed
18.
Khatri P, Bhavsar P, Bawa G, Draghici S. Onto-Tools: an ensemble of web-accessible, ontology-based tools for the functional design and interpretation of high-throughput gene expression experiments. Nucleic Acids Res. 2004;1(32):W449–56. Web Server issue.CrossRef
19.
Catterall A. The natural history of Perthes’ disease. J Bone Joint Surg Br. 1971;53(1):37–53.PubMed
20.
Yang Y, Bu D, Zhao X, Sun P, Wang J, Zhou L. Proteomic analysis of cow, yak, buffalo, goat and camel milk whey proteins: quantitative differential expression patterns. J Proteome Res. 2013;512(4):1660–7.CrossRef
21.
Unwin RD, Griffiths JR, Whetton AD. Simultaneous analysis of relative protein expression levels across multiple samples using iTRAQ isobaric tags with 2D nano LC-MS/MS. Nat Protoc. 2010;5(9):1574–82.CrossRefPubMed
22.
von Mering C, Jensen LJ, Snel B, Hooper SD, Krupp M, Foglierini M, et al. STRING: known and predicted protein-protein associations, integrated and transferred across organisms. Nucleic Acids Res. 2005;1(33):D433–7. Database issue.
23.
Kim SY, Jeoung NH, Oh CJ, Choi YK, Lee HJ, Kim HJ, et al. Activation of NAD (P) H:quinone oxidoreductase 1 prevents arterial restenosis by suppressing vascular smooth muscle cell proliferation. Circ Res. 2009;104(7):842–50.CrossRefPubMed
24.
Okazaki S, Nishitani Y, Nagoya S, Kaya M, Yamashita T, Matsumoto H. Femoral head osteonecrosis can be caused by disruption of the systemic immune response via the toll-like receptor 4 signalling pathway. Rheumatology (Oxford). 2009;48(3):227–32.CrossRef
25.
Srzentić S, Spasovski V, Spasovski D, Zivković Z, Matanović D, Bascarević Z, et al. Association of gene variants in TLR4 and IL-6 genes with Perthes disease. Srp Arh Celok Lek. 2014;142(7–8):450–6.CrossRefPubMed
26.
Wang Q, Rozelle AL, Lepus CM, Scanzello CR, Song JJ, Larsen DM, et al. Identification of a central role for complement in osteoarthritis. Nat Med. 2011;17(12):1674–9.CrossRefPubMedPubMedCentral
27.
John T, Stahel PF, Morgan SJ, Schulze-Tanzil G. Impact of the complement cascade on posttraumatic cartilage inflammation and degradation. Histol Histopathol. 2007;22(7):781–90.PubMed
28.
Zilkens C, Holstein A, Bittersohl B, Jäger M, Haamberg T, Miese F, et al. Delayed gadolinium-enhanced magnetic resonance imaging of cartilage in the long-term follow-up after Perthes disease. J Pediatr Orthop. 2010;30(2):147–53.CrossRefPubMed
29.
Orfanos I, Magkou C, Anastasopoulos I, Karanikas E, Sitaras NM. Urine glycosaminoglycans in children with transient hip synovitis and Perthes disease. J Pediatr Orthop B. 2005;14(2):92–6.CrossRefPubMed
30.
Eckerwall G, Lohmander LS, Wingstrand H. Increased levels of proteoglycan fragments and stromelysin in hip joint fluid in Legg-Calvé-Perthes disease. J Pediatr Orthop. 1997;17(2):266–9.CrossRefPubMed
31.
Zreiqat H, Howlett CR, Gronthos S, Hume D, Geczy CL. S100A8/S100A9 and their association with cartilage and bone. J Mol Histol. 2007;38(5):381–91.CrossRefPubMed
32.
Barksby HE, Hui W, Wappler I, Peters HH, Milner JM, Richards CD, et al. Interleukin-1 in combination with oncostatin M up-regulates multiple genesin chondrocytes:implications for cartilage destruction and repair. Arthritis Rheum. 2006;54:540–50.CrossRefPubMed
33.
Chen F, Kerner MB, Dorfman HD, Hamerman D. The distribution of S-100 protein in articular cartilage from osteoarthritic joints. J Rheumatol. 1990;17(12):1676–81.PubMed
34.
Schelbergen RF, Blom AB, van den Bosch MH, Slöetjes A, Abdollahi-Roodsaz S, Schreurs BW, et al. Alarmins S100A8 and S100A9 elicit a catabolic effect in human osteoarthritic chondrocytes that is dependent on Toll-like receptor 4. Arthritis Rheum. 2012;64(5):1477–87.CrossRefPubMed
35.
Hammer HB, Odegard S, Fagerhol MK, Landewé R, van der Heijde D, Uhlig T, et al. Calprotectin (a major leucocyte protein) is strongly and independently correlated with joint inflammation and damage in rheumatoid arthritis. Ann Rheum Dis. 2007;66(8):1093–7.CrossRefPubMedPubMedCentral
36.
Brun JG, Jonsson R, Haga HJ. Measurement of plasma calprotectin as an indicator of arthritis and disease activity in patients with inflammatory rheumatic diseases. J Rheumatol. 1994;21(4):733–8.PubMed
37.
Hirata T, Fujioka M, Takahashi KA, Arai Y, Asano T, Ishida M, et al. ApoB C7623T polymorphism predicts risk for steroid-induced osteonecrosis of the femoral head after renal transplantation. J Orthop Sci. 2007;12(3):199–206.CrossRefPubMed
38.
Wang XY, Niu XH, Chen WH, Lin N, Song JN, Chen B, et al. [Effects of apolipoprotein A1 and B gene polymorphism on avascular necrosis of the femoral head in Chinese population]. Zhongguo Gu Shang. 2008;21(2):99–102.PubMed
39.
Jones Jr JP. Fat embolism and osteonecrosis. Orthop Clin North Am. 1985;16(4):595–633.PubMed
40.
Rappaport EB, Fife D. Slipped capital femoral epiphysis in growth hormone-deficient patients. Am J Dis Child. 1985;139(4):396–9.PubMed
41.
Kitoh H, Kitakoji T, Kawasumi M, Ishiguro N. A histological and ultrastructural study of the iliac crest apophysis in Legg-Calve-Perthes disease. J Pediatr Orthop. 2008;28(4):435–9.CrossRefPubMed
42.
He W, Li K. Incidence of genetic polymorphisms involved in lipid metabolism among Chinese patients with osteonecrosis of the femoral head. Acta Orthop. 2009;80(3):325–9.CrossRefPubMedPubMedCentral
Metadata
Title
Comparative study of serum proteomes in Legg-Calve-Perthes disease
Authors
Ruiyu Liu
Lihong Fan
Longbin Yin
Kunzheng Wang
Wusheng Miao
Qichun Song
Xiaoqian Dang
Hang Gao
Chuanyi Bai
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2015
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/s12891-015-0730-z

Other articles of this Issue 1/2015

BMC Musculoskeletal Disorders 1/2015 Go to the issue

Research article

The potential risk of spinal cord injury from pedicle screw at the apex of adolescent idiopathic thoracic scoliosis: magnetic resonance imaging evaluation

Research article

Influence of pelvic incidence-lumbar lordosis mismatch on surgical outcomes of short-segment transforaminal lumbar interbody fusion

Research article

Management of hyperlipidemia among patients with rheumatoid arthritis in the primary care setting

Research article

Quadriceps muscle strength, radiographic knee osteoarthritis and knee pain: the ROAD study

Research article

Biologic predictors of clinical improvement in rituximab-treated refractory myositis

Research article

Why we still perform arthroscopy in knee osteoarthritis: a multi-methods study