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01-09-2014 | Original Article

Significant increase of plasma tetranectin in ovx mice as defined by proteomics analysis

Authors: Koichi Sasaki, Yasuhiro Ozasa, Kousuke Iba, Takuro Wada, Shin-ichi Imai, Kayo Matsumoto, Hitoshi Sohma, Masato Aoshima, Toshihiko Yamashita, Yasuo Kokai

Published in: Journal of Orthopaedic Science | Issue 5/2014

Abstract

Background

Proteomics is recognized as a useful tool in the dynamic screening of plasma protein expression. This study aimed to identify increased expressions of novel plasma proteins in ovariectomized mice (ovx) using selective reaction monitoring (SRM) validation in combination with electrospray ionized-quadrupole time-of-flight mass spectrometry (ESI-Q-TOF-MS) screening.

Materials and methods

Twenty-week-old female C57BL/6 mice were ovariectomized or subjected to surgical exposure of the ovaries alone (sham). Blood plasma protein at 4 weeks after these operations was pooled for the ovx and sham group each and separated on SDS–PAGE, and then digested by peptides, which were first differentially displayed by ESI-Q-TOF-MS analysis. Mass spectra of peptides upregulated more than twofold in ovx compared to sham mice were selected for protein identification by ESI-Q-TOF-MS. The selected peptides were further validated in independent samples by SRM using electrospray ionized-triple quadrupole-linear ion trap mass spectrometry (ESI-QqLIT-MS). Optimum transitions for SRM were manually chosen for their high specificity in identifying peptides derived from the candidate proteins.

Results

Differential analysis of peptides revealed 1,108 upregulated peptides in ovx compared with sham control mice. Among the upregulated peptides, 231 nonredundant proteins were identified. Validation analysis for the potential use of these proteins as markers of bone turnover was performed using ESI-QqLIT-MS. The four proteins from the plasma samples, namely mannose-binding lectin-C, major urinary protein 2, type I collagen alpha 2 chain, and tetranectin, were evaluated in a blinded manner. A statistically significant elevation of all four proteins in the plasma of ovx mice was confirmed by SRM. Of the four upregulated plasma proteins, tetranectin increased by almost 50 times in the ovx mice compared with the sham mice.

Conclusions

On the basis of proteomics analysis, this study demonstrated that four plasma proteins were significantly elevated in the ovx mice; of these, tetranectin was markedly upregulated by almost 50 times compared with the sham mice.

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NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy, March 7–29, 2000: highlights of the conference. Southern Med J 2001;94(6):569–73.

Ivaska KK, Gerdhem P, Vaananen HK, Akesson K, Obrant KJ. Bone turnover markers and prediction of fracture: a prospective follow-up study of 1040 elderly women for a mean of 9 years. J Bone Miner Res. 2010;25(2):393–403.PubMedCrossRef

Nishizawa Y, Ohta H, Miura M, Inaba M, Ichimura S, Shiraki M, Takada J, Chaki O, Hagino H, Fujiwara S, Fukunaga M, Miki T, Yoshimura N. Guidelines for the use of bone metabolic markers in the diagnosis and treatment of osteoporosis (2012 edition). J Bone Miner Metab. 2013;31:1–15.PubMedCrossRef

Omenn GS, States DJ, Adamski M, Blackwell TW, Menon R, Hermjakob H, Apweiler R, Haab BB, Simpson RJ, Eddes JS, Kapp EA, Moritz RL, Chan DW, Rai AJ, Admon A, Aebersold R, Eng J, Hancock WS, Hefta SA, Meyer H, Paik YK, Yoo JS, Ping P, Pounds J, Adkins J, Qian X, Wang R, Wasinger V, Wu CY, Zhao X, Zeng R, Archakov A, Tsugita A, Beer I, Pandey A, Pisano M, Andrews P, Tammen H, Speicher DW, Hanash SM. Overview of the HUPO Plasma Proteome Project: results from the pilot phase with 35 collaborating laboratories and multiple analytical groups, generating a core dataset of 3020 proteins and a publicly-available database. Proteomics. 2005;5(13):3226–45.PubMedCrossRef

Etzioni R, Urban N, Ramsey S, McIntosh M, Schwartz S, Reid B, Radich J, Anderson G, Hartwell L. The case for early detection. Nat Rev Cancer. 2003;3(4):243–52.PubMedCrossRef

Hori T, Naishiro Y, Sohma H, Suzuki N, Hatakeyama N, Yamamoto M, Sonoda T, Mizue Y, Imai K, Tsutsumi H, Kokai Y. CCL8 is a potential molecular candidate for the diagnosis of graft-versus-host disease. Blood. 2008;111(8):4403–12.PubMedCrossRefPubMedCentral

Anderson L. Candidate-based proteomics in the search for biomarkers of cardiovascular disease. J Physiol. 2005;563(Pt 1):23–60.PubMedCrossRefPubMedCentral

Anderson L, Hunter CL. Quantitative mass spectrometric multiple reaction monitoring assays for major plasma proteins. Mol Cell Proteomics. 2006;5(4):573–88.PubMedCrossRef

Bhattacharyya S, Siegel ER, Achenbach SJ, Khosla S, Suva LJ. Serum biomarker profile associated with high bone turnover and BMD in postmenopausal women. J Bone Miner Res. 2008;23(7):1106–17.PubMedCrossRefPubMedCentral

10.

Kokai Y, Wada T, Oda T, Kuwabara H, Hara K, Akiyama Y, Ishii S, Sawada N. Overexpression of granulocyte colony-stimulating factor induces severe osteopenia in developing mice that is partially prevented by a diet containing vitamin K2 (menatetrenone). Bone. 2002;30(6):880–5.PubMedCrossRef

11.

Shevchenko A, Wilm M, Vorm O, Mann M. Mass spectrometric sequencing of proteins silver-stained polyacrylamide gels. Anal Chem. 1996;68(5):850–8.PubMedCrossRef

12.

Shilov IV, Seymour SL, Patel AA, Loboda A, Tang WH, Keating SP, Hunter CL, Nuwaysir LM, Schaeffer DA. The Paragon Algorithm, a next generation search engine that uses sequence temperature values and feature probabilities to identify peptides from tandem mass spectra. Mol Cell Proteomics. 2007;6(9):1638–55.PubMedCrossRef

13.

Zhang H, Recker R, Lee WN, Xiao GG. Proteomics in bone research. Expert Rev Proteomics. 2010;7(1):103–11.PubMedCrossRefPubMedCentral

14.

Anderson NL, Anderson NG. The human plasma proteome: history, character, and diagnostic prospects. Mol Cell Proteomics. 2002;1(11):845–67.PubMedCrossRef

15.

Tirumalai RS, Chan KC, Prieto DA, Issaq HJ, Conrads TP, Veenstra TD. Characterization of the low molecular weight human serum proteome. Mol Cell Proteomics. 2003;2(10):1096–103.PubMedCrossRef

16.

Simpson RJ, Connolly LM, Eddes JS, Pereira JJ, Moritz RL, Reid GE. Proteomic analysis of the human colon carcinoma cell line (LIM 1215): development of a membrane protein database. Electrophoresis. 2000;21(9):1707–32.PubMedCrossRef

17.

Pernemalm M, Orre LM, Lengqvist J, Wikstrom P, Lewensohn R, Lehtio J. Evaluation of three principally different intact protein prefractionation methods for plasma biomarker discovery. J Proteome Res. 2008;7(7):2712–22.PubMedCrossRef

18.

Sherman J, McKay MJ, Ashman K, Molloy MP. How specific is my SRM? The issue of precursor and product ion redundancy. Proteomics. 2009;9(5):1120–3.PubMedCrossRef

19.

Mizuno Y, Kozutsumi Y, Kawasaki T, Yamashina I. Isolation and characterization of a mannan-binding protein from rat liver. J Biol Chem. 1981;256(9):4247–52.PubMed

20.

Holmskov U, Malhotra R, Sim RB, Jensenius JC. Collectins: collagenous C-type lectins of the innate immune defense system. Immunol Today. 1994;15(2):67–74.PubMedCrossRef

21.

Santiago-Garcia J, Kodama T, Pitas RE. The class A scavenger receptor binds to proteoglycans and mediates adhesion of macrophages to the extracellular matrix. J Biol Chem. 2003;278(9):6942–6.PubMedCrossRef

22.

Fisher LW, Termine JD, Young MF. Deduced protein sequence of bone small proteoglycan I (biglycan) shows homology with proteoglycan II (decorin) and several nonconnective tissue proteins in a variety of species. J Biol Chem. 1989;264(8):4571–6.PubMed

23.

Pagh R, Duus K, Laursen I, Hansen PR, Mangor J, Thielens N, Arlaud GJ, Kongerslev L, Hojrup P, Houen G. The chaperone and potential mannan-binding lectin (MBL) co-receptor calreticulin interacts with MBL through the binding site for MBL-associated serine proteases. FEBS J. 2008;275(3):515–26.PubMedCrossRef

24.

Finlayson JS, Potter M, Runner CR. Electrophoretic variation and sex dimorphism of the major urinary protein complex in inbred mice: a new genetic marker. J Natl Cancer Inst. 1963;31:91–107.PubMed

25.

Szoka PR, Paigen K. Regulation of mouse major urinary protein production by the Mup-A gene. Genetics. 1978;90(3):597–612.PubMedPubMedCentral

26.

Clemmensen I, Petersen LC, Kluft C. Purification and characterization of a novel, oligomeric, plasminogen kringle 4 binding protein from human plasma: tetranectin. Eur J Biochem/FEBS. 1986;156(2):327–33.CrossRef

27.

Wewer UM, Ibaraki K, Schjorring P, Durkin ME, Young MF, Albrechtsen R. A potential role for tetranectin in mineralization during osteogenesis. J Cell Biol. 1994;127(6 Pt 1):1767–75.PubMedCrossRef

28.

Iba K, Durkin ME, Johnsen L, Hunziker E, Damgaard-Pedersen K, Zhang H, Engvall E, Albrechtsen R, Wewer UM. Mice with a targeted deletion of the tetranectin gene exhibit a spinal deformity. Mol Cell Biol. 2001;21(22):7817–25.PubMedCrossRefPubMedCentral

29.

Iba K, Abe Y, Chikenji T, Kanaya K, Chiba H, Sasaki K, Dohke T, Wada T, Yamashita T. Delayed fracture healing in tetranectin-deficient mice. J Bone Miner Metab. 2013;31:399–408.PubMedCrossRef

30.

Jensen BA, Clemmensen I. Plasma tetranectin is reduced in cancer and related to metastasia. Cancer. 1988;62(5):869–72.PubMedCrossRef

31.

Høgdall CK. Human tetranectin: methodological and clinical studies. APMIS Suppl. 1998;86:1–31.PubMed

Title: Significant increase of plasma tetranectin in ovx mice as defined by proteomics analysis
Authors: Koichi Sasaki
Yasuhiro Ozasa
Kousuke Iba
Takuro Wada
Shin-ichi Imai
Kayo Matsumoto
Hitoshi Sohma
Masato Aoshima
Toshihiko Yamashita
Yasuo Kokai
Publication date: 01-09-2014
Publisher: Springer Japan
Published in: Journal of Orthopaedic Science / Issue 5/2014
Print ISSN: 0949-2658
Electronic ISSN: 1436-2023
DOI: https://doi.org/10.1007/s00776-014-0586-3

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Significant increase of plasma tetranectin in ovx mice as defined by proteomics analysis

Abstract

Background

Materials and methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Materials and methods

Results

Conclusions

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