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Osteoporosis International

Erschienen in:

09.02.2019 | Original Article

Differentially expressed proteins identified by TMT proteomics analysis in bone marrow microenvironment of osteoporotic patients

verfasst von: Q. Zhou, F. Xie, B. Zhou, J. Wang, B. Wu, L. Li, Y. Kang, R. Dai, Y. Jiang

Erschienen in: Osteoporosis International | Ausgabe 5/2019

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Abstract

Summary

We applied tandem mass tag (TMT)-based proteomics to investigate protein changes in bone marrow microenvironment of osteoporotic patients undergoing spine fusion. Multiple bioinformatics tools were used to identify and analyze 219 differentially expressed proteins. These proteins may be associated with the pathogenesis of osteoporosis.

Introduction

Bone marrow microenvironment is indispensable for the maintenance of bone homeostasis. We speculated that alterations of some factors in the microenvironment of osteoporotic subjects might influence the homeostasis. This study aimed to investigate the changes in the expression of protein factors in the bone marrow environment of osteoporosis.

Methods

We performed a proteomics analysis in the vertebral body-derived bone marrow supernatant fluid from 8 Chinese patients undergoing posterior lumbar interbody fusion (4 osteoporotic vs. 4 non-osteoporotic) and used micro-CT to analyze the microstructural features of spinous processes from these patients. We further performed western blotting to validate the differential expressions of some proteins.

Results

There was deteriorated bone microstructure in osteoporotic patients. Based on proteomics analysis, 172 upregulated and 47 downregulated proteins were identified. These proteins had multiple biological functions associated with osteoblast differentiation, lipid metabolism, and cell migration, and formed a complex protein–protein interaction network. We identified five major regulatory mechanisms, splicing, translation, protein degradation, cytoskeletal organization, and lipid metabolism, involved in the pathogenesis of osteoporosis.

Conclusions

There are various protein factors, such as DDX5, PSMC2, CSNK1A1, PLIN1, ILK, and TPM4, differentially expressed in the bone marrow microenvironment of osteoporotic patients, providing new ideas for finding therapeutic targets for osteoporosis.

Rachner TD, Khosla S, Hofbauer LC (2011) Osteoporosis: now and the future. Lancet 377(9773):1276–1287. https://doi.org/10.1016/S0140-6736(10)62349-5 CrossRefPubMedPubMedCentral

Collin-Osdoby P (1994) Role of vascular endothelial cells in bone biology. J Cell Biochem 55(3):304–309. https://doi.org/10.1002/jcb.240550306 CrossRefPubMed

Li J, Liu X, Zuo B, Zhang L (2016) The role of bone marrow microenvironment in governing the balance between osteoblastogenesis and adipogenesis. Aging Dis 7(4):514–525. https://doi.org/10.14336/AD.2015.1206 CrossRefPubMed

Feng X, McDonald JM (2011) Disorders of bone remodeling. Annu Rev Pathol 6:121–145. https://doi.org/10.1146/annurev-pathol-011110-130203 CrossRefPubMedPubMedCentral

Moore KA, Lemischka IR (2006) Stem cells and their niches. Science 311(5769):1880–1885. https://doi.org/10.1126/science.1110542 CrossRefPubMed

Bai XC, Lu D, Bai J, Zheng H, Ke ZY, Li XM, Luo SQ (2004) Oxidative stress inhibits osteoblastic differentiation of bone cells by ERK and NF-kappaB. Biochem Biophys Res Commun 314(1):197–207CrossRefPubMed

Gillet C, Dalla Valle A, Gaspard N, Spruyt D, Vertongen P, Lechanteur J, Rigutto S, Dragan ER, Heuschling A, Gangji V, Rasschaert J (2017) Osteonecrosis of the femoral head: lipotoxicity exacerbation in MSC and modifications of the bone marrow fluid. Endocrinology 158(3):490–502. https://doi.org/10.1210/en.2016-1687 CrossRefPubMed

Elbaz A, Wu X, Rivas D, Gimble JM, Duque G (2010) Inhibition of fatty acid biosynthesis prevents adipocyte lipotoxicity on human osteoblasts in vitro. J Cell Mol Med 14(4):982–991. https://doi.org/10.1111/j.1582-4934.2009.00751.x CrossRefPubMed

Xie F, Zhou B, Wang J, Liu T, Wu X, Fang R, Kang Y, Dai R (2018) Microstructural properties of trabecular bone autografts: comparison of men and women with and without osteoporosis. Arch Osteoporos 13(1):18. https://doi.org/10.1007/s11657-018-0422-z CrossRefPubMed

10.

Zeng Y, Zhang L, Zhu W, He H, Sheng H, Tian Q, Deng FY, Zhang LS, Hu HG, Deng HW (2017) Network based subcellular proteomics in monocyte membrane revealed novel candidate genes involved in osteoporosis. Osteoporos Int 28(10):3033–3042. https://doi.org/10.1007/s00198-017-4146-5 CrossRefPubMedPubMedCentral

11.

Nielson CM, Wiedrick J, Shen J, Jacobs J, Baker ES, Baraff A, Piehowski P, Lee CG, Baratt A, Petyuk V, McWeeney S, Lim JY, Bauer DC, Lane NE, Cawthon PM, Smith RD, Lapidus J, Orwoll ES, Osteoporotic Fractures in Men Study Research G (2017) Identification of hip BMD loss and fracture risk markers through population-based serum proteomics. J Bone Miner Res 32(7):1559–1567. https://doi.org/10.1002/jbmr.3125 CrossRefPubMed

12.

Zhu W, Shen H, Zhang JG, Zhang L, Zeng Y, Huang HL, Zhao YC, He H, Zhou Y, Wu KH, Tian Q, Zhao LJ, Deng FY, Deng HW (2017) Cytosolic proteome profiling of monocytes for male osteoporosis. Osteoporos Int 28(3):1035–1046. https://doi.org/10.1007/s00198-016-3825-y CrossRefPubMed

13.

Zhang L, Liu YZ, Zeng Y, Zhu W, Zhao YC, Zhang JG, Zhu JQ, He H, Shen H, Tian Q, Deng FY, Papasian CJ, Deng HW (2016) Network-based proteomic analysis for postmenopausal osteoporosis in Caucasian females. Proteomics 16(1):12–28. https://doi.org/10.1002/pmic.201500005 CrossRefPubMed

14.

Xie Y, Gao Y, Zhang L, Chen Y, Ge W, Tang P (2018) Involvement of serum-derived exosomes of elderly patients with bone loss in failure of bone remodeling via alteration of exosomal bone-related proteins. Aging Cell 17(3):e12758. https://doi.org/10.1111/acel.12758 CrossRefPubMedPubMedCentral

15.

Miranda M, Pino AM, Fuenzalida K, Rosen CJ, Seitz G, Rodriguez JP (2016) Characterization of fatty acid composition in bone marrow fluid from postmenopausal women: modification after hip fracture. J Cell Biochem 117(10):2370–2376. https://doi.org/10.1002/jcb.25534 CrossRefPubMedPubMedCentral

16.

Pino AM, Rios S, Astudillo P, Fernandez M, Figueroa P, Seitz G, Rodriguez JP (2010) Concentration of adipogenic and proinflammatory cytokines in the bone marrow supernatant fluid of osteoporotic women. J Bone Miner Res 25(3):492–498. https://doi.org/10.1359/jbmr.090802 CrossRefPubMed

17.

Wiig H, Berggreen E, Borge BA, Iversen PO (2004) Demonstration of altered signaling responses in bone marrow extracellular fluid during increased hematopoiesis in rats using a centrifugation method. Am J Physiol Heart Circ Physiol 286(5):H2028–H2034. https://doi.org/10.1152/ajpheart.00934.2003 CrossRefPubMed

18.

Moulder R, Bhosale SD, Goodlett DR, Lahesmaa R (2017) Analysis of the plasma proteome using iTRAQ and TMT-based isobaric labeling. Mass Spectrom Rev 37:583–606. https://doi.org/10.1002/mas.21550 CrossRefPubMed

19.

Thompson A, Schafer J, Kuhn K, Kienle S, Schwarz J, Schmidt G, Neumann T, Johnstone R, Mohammed AK, Hamon C (2003) Tandem mass tags: a novel quantification strategy for comparative analysis of complex protein mixtures by MS/MS. Anal Chem 75(8):1895–1904CrossRefPubMed

20.

Chabot B, Shkreta L (2016) Defective control of pre-messenger RNA splicing in human disease. J Cell Biol 212(1):13–27. https://doi.org/10.1083/jcb.201510032 CrossRefPubMedPubMedCentral

21.

Dejaeger M, Bohm AM, Dirckx N, Devriese J, Nefyodova E, Cardoen R, St-Arnaud R, Tournoy J, Luyten FP, Maes C (2017) Integrin-linked kinase regulates bone formation by controlling cytoskeletal organization and modulating BMP and Wnt signaling in Osteoprogenitors. J Bone Miner Res 32(10):2087–2102. https://doi.org/10.1002/jbmr.3190 CrossRefPubMed

22.

Higuchi C, Nakamura N, Yoshikawa H, Itoh K (2009) Transient dynamic actin cytoskeletal change stimulates the osteoblastic differentiation. J Bone Miner Metab 27(2):158–167. https://doi.org/10.1007/s00774-009-0037-y CrossRefPubMed

23.

Novack DV, Faccio R (2011) Osteoclast motility: putting the brakes on bone resorption. Ageing Res Rev 10(1):54–61. https://doi.org/10.1016/j.arr.2009.09.005 CrossRefPubMed

24.

Wang F, Canadeo LA, Huibregtse JM (2015) Ubiquitination of newly synthesized proteins at the ribosome. Biochimie 114:127–133. https://doi.org/10.1016/j.biochi.2015.02.006 CrossRefPubMedPubMedCentral

25.

Schaefer A, Nethe M, Hordijk PL (2012) Ubiquitin links to cytoskeletal dynamics, cell adhesion and migration. Biochem J 442(1):13–25. https://doi.org/10.1042/BJ20111815 CrossRefPubMed

26.

Gravina GL, Tortoreto M, Mancini A, Addis A, Di Cesare E, Lenzi A, Landesman Y, McCauley D, Kauffman M, Shacham S, Zaffaroni N, Festuccia C (2014) XPO1/CRM1-selective inhibitors of nuclear export (SINE) reduce tumor spreading and improve overall survival in preclinical models of prostate cancer (PCa). J Hematol Oncol 7:46. https://doi.org/10.1186/1756-8722-7-46 CrossRefPubMedPubMedCentral

27.

Ramanathan N, Lim N, Stewart CL (2015) DDX5/p68 RNA helicase expression is essential for initiating adipogenesis. Lipids Health Dis 14:160. https://doi.org/10.1186/s12944-015-0163-6 CrossRefPubMedPubMedCentral

28.

Jensen ED, Niu L, Caretti G, Nicol SM, Teplyuk N, Stein GS, Sartorelli V, van Wijnen AJ, Fuller-Pace FV, Westendorf JJ (2008) p68 (Ddx5) interacts with Runx2 and regulates osteoblast differentiation. J Cell Biochem 103(5):1438–1451. https://doi.org/10.1002/jcb.21526 CrossRefPubMed

29.

Kumar Y, Kapoor I, Khan K, Thacker G, Khan MP, Shukla N, Kanaujiya JK, Sanyal S, Chattopadhyay N, Trivedi AK (2015) E3 ubiquitin ligase Fbw7 negatively regulates osteoblast differentiation by targeting Runx2 for degradation. J Biol Chem 290(52):30975–30987. https://doi.org/10.1074/jbc.M115.669531

30.

Calviello G, Resci F, Serini S, Piccioni E, Toesca A, Boninsegna A, Monego G, Ranelletti FO, Palozza P (2007) Docosahexaenoic acid induces proteasome-dependent degradation of beta-catenin, down-regulation of survivin and apoptosis in human colorectal cancer cells not expressing COX-2. Carcinogenesis 28(6):1202–1209. https://doi.org/10.1093/carcin/bgl254 CrossRefPubMed

31.

Kimelman D, Xu W (2006) Beta-catenin destruction complex: insights and questions from a structural perspective. Oncogene 25(57):7482–7491. https://doi.org/10.1038/sj.onc.1210055 CrossRefPubMed

32.

Brakebusch C, Fassler R (2003) The integrin-actin connection an eternal love affair. EMBO J 22(10):2324–2333. https://doi.org/10.1093/emboj/cdg245 CrossRefPubMedPubMedCentral

33.

Dossa T, Arabian A, Windle JJ, Dedhar S, Teitelbaum SL, Ross FP, Roodman GD, St-Arnaud R (2010) Osteoclast-specific inactivation of the integrin-linked kinase (ILK) inhibits bone resorption. J Cell Biochem 110(4):960–967. https://doi.org/10.1002/jcb.22609 CrossRefPubMedPubMedCentral

34.

Gimona M, Kazzaz JA, Helfman DM (1996) Forced expression of tropomyosin 2 or 3 in v-Ki-ras-transformed fibroblasts results in distinct phenotypic effects. Proc Natl Acad Sci U S A 93(18):9618–9623CrossRefPubMedPubMedCentral

35.

McMichael BK, Kotadiya P, Singh T, Holliday LS, Lee BS (2006) Tropomyosin isoforms localize to distinct microfilament populations in osteoclasts. Bone 39(4):694–705. https://doi.org/10.1016/j.bone.2006.04.031 CrossRefPubMed

36.

McMichael BK, Lee BS (2008) Tropomyosin 4 regulates adhesion structures and resorptive capacity in osteoclasts. Exp Cell Res 314(3):564–573. https://doi.org/10.1016/j.yexcr.2007.10.018 CrossRefPubMed

37.

Fazeli PK, Horowitz MC, MacDougald OA, Scheller EL, Rodeheffer MS, Rosen CJ, Klibanski A (2013) Marrow fat and bone—new perspectives. J Clin Endocrinol Metab 98(3):935–945. https://doi.org/10.1210/jc.2012-3634 CrossRefPubMedPubMedCentral

38.

Brasaemle DL (2007) Thematic review series: adipocyte biology. The perilipin family of structural lipid droplet proteins: stabilization of lipid droplets and control of lipolysis. J Lipid Res 48(12):2547–2559. https://doi.org/10.1194/jlr.R700014-JLR200

39.

Grahn TH, Zhang Y, Lee MJ, Sommer AG, Mostoslavsky G, Fried SK, Greenberg AS, Puri V (2013) FSP27 and PLIN1 interaction promotes the formation of large lipid droplets in human adipocytes. Biochem Biophys Res Commun 432(2):296–301. https://doi.org/10.1016/j.bbrc.2013.01.113 CrossRefPubMedPubMedCentral

40.

Lehman RA Jr, Kang DG, Wagner SC (2015) Management of osteoporosis in spine surgery. J Am Acad Orthop Surg 23(4):253–263. https://doi.org/10.5435/JAAOS-D-14-00042 CrossRefPubMed

Titel: Differentially expressed proteins identified by TMT proteomics analysis in bone marrow microenvironment of osteoporotic patients
verfasst von: Q. Zhou
F. Xie
B. Zhou
J. Wang
B. Wu
L. Li
Y. Kang
R. Dai
Y. Jiang
Publikationsdatum: 09.02.2019
Verlag: Springer London
Erschienen in: Osteoporosis International / Ausgabe 5/2019
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-019-04884-0

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Differentially expressed proteins identified by TMT proteomics analysis in bone marrow microenvironment of osteoporotic patients

Abstract

Summary

Introduction

Methods

Results

Conclusions

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Abstract

Summary

Introduction

Methods

Results

Conclusions

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