Skip to main content
SpringerLink
Log in

Gender-specific SBNO2 and VPS13B as a potential driver of osteoporosis development in male ankylosing spondylitis

  • Original Article
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

Summary

To identify the critical genes and pathways that related to OP development in male AS patients, bioinformatic gene analysis and qRT-PCR validation were performed. SBNO2 and VPS13B were identified as the potential target for OP development, which may be valuable for the prevention of OP in male AS patients.

Introduction

Osteoporosis (OP) is common in men with ankylosing spondylitis (AS). The specific pathogenesis of OP in AS, however, is still unclear. The present study attempted to identify potential genes associated with the development of OP in males with AS.

Methods

Gene expression profiles were downloaded from the GSE73754 and GSE35959 datasets from the Gene Expression Omnibus (GEO). Data from OsteoporosAtlas were downloaded as a supplement. Differentially expressed genes (DEGs) were determined with the limma package. The overlapping DEGs between male AS-related genes and OP-related genes were determined. The DEGs were validated by qRT-PCR in the blood samples of males with AS. Weighted gene co-expression network analysis (WGCNA) was utilized to establish a co-expression network to identify the hub genes.

Results

A total of 17 overlapping DEGs were identified; 6 genes in 17 overlapping DEGs were verified as the essential genes in the pathogenesis of OP in male AS by qRT-PCR analysis. After WGCNA, the modules of MEblue (> 0.6) and MEred (> 0.8) were screened out by the correlation analysis and were determined to function mainly in MAPK signaling pathway and osteoclast differentiation. Analysis of the two modules revealed VPS13B and SBNO2 as key genes due to the high degree of correlation. Both genes play an important role in bone metabolism regulation in male AS. Two hub genes MYD88 in MEblue and NCK1 in MEred with high degree of connectivity were selected.

Conclusions

Gender-specific SBNO2 and VPS13B may be key genes involved in OP in male AS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

OP:

Osteoporosis

AS:

Ankylosing spondylitis

GEO:

Gene Expression Omnibus

DEGs:

Differential expression genes

qRT-PCR:

Quantitative reverse transcriptase-polymerase chain reaction

BMD:

Bone mineral density

WGCNA:

Construction of weighted gene co-expression network analysis

GO:

Gene Ontology

KEGG:

Kyoto Encyclopedia of Genes and Genomes

FNCSGPs:

Femoral neck cross-sectional geometric parameters

TAL1:

T cell acute lymphoblastic leukemia 1

MITF:

Microphthalmia-associated transcription factor

MAPK:

Mitogen-activated protein kinase

BMP:

Bone morphogenetic protein

DC-STAMP:

Dendritic cell-specific transmembrane protein

References

  1. Klingberg E, Nurkkala M, Carlsten H, Forsblad-d’Elia H (2014) Biomarkers of bone metabolism in ankylosing spondylitis in relation to osteoproliferation and osteoporosis. J Rheumatol 41:1349–1356

    Article  Google Scholar 

  2. Bessant R, Keat A (2002) How should clinicians manage osteoporosis in ankylosing spondylitis? J Rheumatol 29:1511–1519

    PubMed  Google Scholar 

  3. Magrey M, Khan MA (2010) Osteoporosis in ankylosing spondylitis. Curr Rheumatol Rep 12:332–336

    Article  Google Scholar 

  4. Devogelaer JP, Maldague B, Malghem J, Nagant de Deuxchaisnes C (1992) Appendicular and vertebral bone mass in ankylosing spondylitis. A comparison of plain radiographs with single- and dual-photon absorptiometry and with quantitative computed tomography. Arthritis Rheum 35:1062–1067

    Article  CAS  Google Scholar 

  5. Vasdev V, Bhakuni D, Garg MK, Narayanan K, Jain R, Chadha D (2011) Bone mineral density in young males with ankylosing spondylitis. Int J Rheum Dis 14:68–73

    Article  Google Scholar 

  6. Karberg K, Zochling J, Sieper J, Felsenberg D, Braun J (2005) Bone loss is detected more frequently in patients with ankylosing spondylitis with syndesmophytes. J Rheumatol 32:1290–1298

    PubMed  Google Scholar 

  7. Lange U, Kluge A, Strunk J, Teichmann J, Bachmann G (2005) Ankylosing spondylitis and bone mineral density--what is the ideal tool for measurement? Rheumatol Int 26:115–120

    Article  Google Scholar 

  8. Magrey MN, Lewis S, Asim Khan M (2016) Utility of DXA scanning and risk factors for osteoporosis in ankylosing spondylitis-a prospective study. Semin Arthritis Rheum 46:88–94

    Article  Google Scholar 

  9. Hu LY, Lu T, Chen PM, Shen CC, Hung YM, Hsu CL (2019) Should clinicians pay more attention to the potential underdiagnosis of osteoporosis in patients with ankylosing spondylitis? A national population-based study in Taiwan. PLoS One 14:e0211835

    Article  CAS  Google Scholar 

  10. Meirelles ES, Borelli A, Camargo OP (1999) Influence of disease activity and chronicity on ankylosing spondylitis bone mass loss. Clin Rheumatol 18:364–368

    Article  CAS  Google Scholar 

  11. Franck H, Meurer T, Hofbauer LC (2004) Evaluation of bone mineral density, hormones, biochemical markers of bone metabolism, and osteoprotegerin serum levels in patients with ankylosing spondylitis. J Rheumatol 31:2236–2241

    CAS  PubMed  Google Scholar 

  12. Wang X, Diao L, Sun D, Wang D, Zhu J, He Y, Liu Y, Xu H, Zhang Y, Liu J, Wang Y, He F, Li Y, Li D (2019) OsteoporosAtlas: a human osteoporosis-related gene database. PeerJ 7:e6778

    Article  Google Scholar 

  13. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods (San Diego, Calif) 25:402–408

    Article  CAS  Google Scholar 

  14. Moll JM (1987) New criteria for the diagnosis of ankylosing spondylitis. Scand J Rheumatol Suppl 65:12–24

    Article  CAS  Google Scholar 

  15. Xu XM, Li N, Li K, Li XY, Zhang P, Xuan YJ, Cheng XG (2019) Discordance in diagnosis of osteoporosis by quantitative computed tomography and dual-energy X-ray absorptiometry in Chinese elderly men. J Orthop Transl 18:59–64

    Google Scholar 

  16. Kirsten ML, Baron RA, Seabra MC, Ces O (2013) Rab1a and Rab5a preferentially bind to binary lipid compositions with higher stored curvature elastic energy. Mol Membr Biol 30:303–314

    Article  CAS  Google Scholar 

  17. Kreivi JP, Trinkle-Mulcahy L, Lyon CE, Morrice NA, Cohen P, Lamond AI (1997) Purification and characterisation of p99, a nuclear modulator of protein phosphatase 1 activity. FEBS Lett 420:57–62

    Article  CAS  Google Scholar 

  18. Maruyama K, Uematsu S, Kondo T, Takeuchi O, Martino MM, Kawasaki T, Akira S (2013) Strawberry notch homologue 2 regulates osteoclast fusion by enhancing the expression of DC-STAMP. J Exp Med 210:1947–1960

    Article  CAS  Google Scholar 

  19. Vaquerizas JM, Kummerfeld SK, Teichmann SA, Luscombe NM (2009) A census of human transcription factors: function, expression and evolution. Nat Rev Genet 10:252–263

    Article  CAS  Google Scholar 

  20. Bordeleau ME, Aucagne R, Chagraoui J, Girard S, Mayotte N, Bonneil É, Thibault P, Pabst C, Bergeron A, Barabé F, Hébert J, Sauvageau M, Boutonnet C, Meloche S, Sauvageau G (2014) UBAP2L is a novel BMI1-interacting protein essential for hematopoietic stem cell activity. Blood 124:2362–2369

    Article  CAS  Google Scholar 

  21. Da Costa R, Bordessoules M, Guilleman M et al (2020) Vps13b is required for acrosome biogenesis through functions in Golgi dynamic and membrane trafficking. Cell Mol Life Sci 77:511–529

    Article  Google Scholar 

  22. Vijayan V, Khandelwal M, Manglani K, Gupta S, Surolia A (2014) Methionine down-regulates TLR4/MyD88/NF-kappaB signalling in osteoclast precursors to reduce bone loss during osteoporosis. Br J Pharmacol 171:107–121

    Article  CAS  Google Scholar 

  23. Aryal ACS, Miyai K, Izu Y, Hayata T, Notomi T, Noda M, Ezura Y (2015) Nck influences preosteoblastic/osteoblastic migration and bone mass. Proc Natl Acad Sci U S A 112:15432–15437

    Article  Google Scholar 

  24. Gracey E, Yao Y, Green B, Qaiyum Z, Baglaenko Y, Lin A, Anton A, Ayearst R, Yip P, Inman RD (2016) Sexual dimorphism in the Th17 signature of ankylosing spondylitis. Arthritis Rheumatol (Hoboken, NJ) 68:679–689

    Article  CAS  Google Scholar 

  25. Sun Y, Liu WZ, Liu T, Feng X, Yang N, Zhou HF (2015) Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis. J Recept Signal Transduct Res 35:600–604

    Article  CAS  Google Scholar 

  26. Kim HK, Kim MG, Leem KH (2014) Effects of egg yolk-derived peptide on osteogenic gene expression and MAPK activation. Molecules (Basel, Switzerland) 19:12909–12924

    Article  Google Scholar 

  27. Kim DY, Kim GW, Chung SH (2013) Nectandrin A enhances the BMP-induced osteoblastic differentiation and mineralization by activation of p38 MAPK-Smad signaling pathway. Korean J Physiol Pharmacol 17:447–453

    Article  CAS  Google Scholar 

  28. Deng FY, Zhao LJ, Pei YF, Sha BY, Liu XG, Yan H, Wang L, Yang TL, Recker RR, Papasian CJ, Deng HW (2010) Genome-wide copy number variation association study suggested VPS13B gene for osteoporosis in Caucasians. Osteoporos Int 21:579–587

    Article  CAS  Google Scholar 

Download references

Funding

This study was funded by the National Natural Science Foundation of China (Grant No. 8197090753), the Application of Clinical Features of Capital City of Science and Technology Commission China BEIJING Special subject (Z181100001718180), and Medical big data and artificial intelligence of PLA General Hospital research project (2019MBD-022).

Author information

Author notes

  1. T. Li, W.-B. Liu, F.-F. Tian and J.-J. Jiang contributed equally to this work.

Authors and Affiliations

  1. Department of Orthopedics, the First Medical Centre, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China

    T. Li, W.-B. Liu, Q. Wang, F.-Q. Hu, W.-H. Hu & X.-S. Zhang

  2. Clinical Biobank Center, the Medical Innovation Research Division, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China

    F.-F. Tian & J.-J. Jiang

  3. Department of Orthopedics, the Fourth Medical Centre, Chinese PLA General Hospital, 51 Fucheng Road, Haidian District, Beijing, 100000, China

    W.-H. Hu

Authors
  1. T. Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. W.-B. Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F.-F. Tian
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J.-J. Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Q. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. F.-Q. Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. W.-H. Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. X.-S. Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to W.-H. Hu or X.-S. Zhang.

Ethics declarations

The study was approved by the Ethics Committee of the Chinese PLA General Hospital and have been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Conflicts of interest

None.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOCX 14 kb)

ESM 2

(DOCX 14 kb)

ESM 3

(DOCX 15 kb)

ESM 4

(DOCX 15 kb)

ESM 5

(DOCX 14 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, T., Liu, WB., Tian, FF. et al. Gender-specific SBNO2 and VPS13B as a potential driver of osteoporosis development in male ankylosing spondylitis. Osteoporos Int 32, 311–320 (2021). https://doi.org/10.1007/s00198-020-05593-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-020-05593-9

Keywords

Search

Navigation