Top

BMC Musculoskeletal Disorders

Published in:

01-12-2020 | Back Pain | Research article

Correlation between the HIF-1α/Notch signaling pathway and Modic changes in nucleus pulposus cells isolated from patients with low back pain

Authors: Zekang Xiong, Jun Ding, Jinge Zhou, Sheng Yao, Jin Zheng, Xiaodong Guo

Published in: BMC Musculoskeletal Disorders | Issue 1/2020

Abstract

Background

The HIF-1α/Notch signaling pathway regulates cell proliferation, apoptosis, and metabolism in the intervertebral discs (IVDs) and is implicated in disc degeneration. The nucleus pulposus (NP) is an important structure adjacent to the IVDs. However, the role of the HIF-1α/Notch signaling pathway in NP cells obtained from patients with different Modic changes (MCs) remains unclear. The purpose of the present study was to investigate the role of HIF-1α and components of the Notch pathway in the NP obtained from patients with various MCs.

Methods

A total of 85 NP tissue samples were collected from patients undergoing diskectomy for the treatment of low back pain. The NP tissues were divided into four groups based on the adjacent endplate degeneration, namely, MC I, II, III, and negative MC groups. The expression of HIF-1α and Notch-related components was measured and compared.

Results

The expression of HIF-1α, Notch1, and Notch2 was gradually increased in the MC I and MC II groups compared with that in the negative MC group. HIF-1α and Notch-related components were rarely detected in the MC III group.

Conclusions

The expression of HIF-1α/Notch increased in the NP cells of patients with MC I and MC II. HIF-1α and Notch-related components are potential biomarkers and the HIF-1α/Notch signaling pathway may serve as a promising therapeutic target for disc degeneration in patients with MCs.

Available only for authorised users

Modic MT, Steinberg PM, Ross JS, Masaryk TJ, Carter JR. Degenerative disk disease: assessment of changes in vertebral body marrow with MR imaging. Radiology. 1988;166(1 Pt 1):193–9.PubMedCrossRef

Modic MT, Masaryk TJ, Ross JS, Carter JR. Imaging of degenerative disk disease. Radiology. 1988;168(1):177–86.PubMedCrossRef

Vital JM, Gille O, Pointillart V, Pedram M, Bacon P, Razanabola F, Schaelderle C, Azzouz S. Course of Modic 1 six months after lumbar posterior osteosynthesis. Spine. 2003;28(7):715–20.PubMed

Schmid G, Witteler A, Willburger R, Kuhnen C, Jergas M, Koester O. Lumbar disk herniation: correlation of histologic findings with marrow signal intensity changes in vertebral endplates at MR imaging. Radiology. 2004;231(2):352–8.PubMedCrossRef

Hansson T, Roos B. Microcalluses of the trabeculae in lumbar vertebrae and their relation to the bone mineral content. Spine. 1981;6(4):375–80.PubMedCrossRef

Crock HV. Internal disc disruption. A challenge to disc prolapse fifty years on. Spine. 1986;11(6):650–3.PubMedCrossRef

Boskey AL. Signaling in response to hypoxia and Normoxia in the intervertebral disc. Arthritis Rheum. 2008;58(12):3637–9.PubMedCrossRef

Semenza GL. Signal transduction to hypoxia-inducible factor 1. Biochem Pharmacol. 2002;64(5–6):993–8.PubMedCrossRef

Kaufman B, Scharf O, Arbeit J, Ashcroft M, Brown JM, Bruick RK, Chapman JD, Evans SM, Giaccia AJ, Harris AL, et al. Proceedings of the oxygen homeostasis/hypoxia meeting. Cancer Res. 2004;64(9):3350–6.PubMedCrossRef

10.

Risbud MV, Schipani E, Shapiro IM. Hypoxic regulation of nucleus Pulposus cell survival from niche to notch. Am J Pathol. 2010;176(4):1577–83.PubMedPubMedCentralCrossRef

11.

Risbud MV, Guttapalli A, Stokes DG, Hawkins D, Danielson KG, Schaer TP, Albert TJ, Shapiro IM. Nucleus pulposus cells express HIF-1 alpha under normoxic culture conditions: a metabolic adaptation to the intervertebral disc microenvironment. J Cell Biochem. 2006;98(1):152–9.PubMedCrossRef

12.

Hiyama A, Skubutyte R, Markova D, Anderson DG, Yadla S, Sakai D, Mochida J, Albert TJ, Shapiro IM, Risbud MV. Hypoxia activates the notch signaling pathway in cells of the intervertebral disc Implications in degenerative disc disease. Arthritis Rheum. 2011;63(5):1355–64.PubMedPubMedCentralCrossRef

13.

Zou J, Li P, Lu F, Liu N, Dai JJ, Ye JJ, Qu X, Sun XL, Ma DX, Park J, et al. Notch1 is required for hypoxia-induced proliferation, invasion and chemoresistance of T-cell acute lymphoblastic leukemia cells. J Hematol Oncol. 2013;6:13.CrossRef

14.

Wang XM, Mao XO, Xie L, Greenberg DA, Jin KL. Involvement of Notch1 signaling in neurogenesis in the subventricular zone of normal and ischemic rat brain in vivo. J Cereb Blood Flow Metab. 2009;29(10):1644–54.PubMedPubMedCentralCrossRef

15.

Wang H, Tian Y, Wang JR, Phillips KLE, Binch ALA, Dunn S, Cross A, Chiverton N, Zheng ZM, Shapiro IM, et al. Inflammatory cytokines induce NOTCH signaling in nucleus Pulposus cells IMPLICATIONS IN INTERVERTEBRAL DISC DEGENERATION. J Biol Chem. 2013;288(23):16761–74.PubMedPubMedCentralCrossRef

16.

Choi H, Merceron C, Mangiavini L, Seifert EL, Schipani E, Shapiro IM, Risbud MV. Hypoxia promotes noncanonical autophagy in nucleus pulposus cells independent of MTOR and HIF1A signaling. Autophagy. 2016;12(9):1631–46.PubMedPubMedCentralCrossRef

17.

Wenger RH, Gassmann M. Oxygen(es) and the hypoxia-inducible factor-1. Biol Chem. 1997;378(7):609–16.PubMed

18.

Sahlgren C, Gustafsson MV, Jin S, Poellinger L, Lendahl U. Notch signaling mediates hypoxia-induced tumor cell migration and invasion. Proc Natl Acad Sci U S A. 2008;105(17):6392–7.PubMedPubMedCentralCrossRef

19.

Wang RS, Zhang YW, Zhang X, Liu RZ, Zhang X, Hong SG, Xia K, Xia JH, Zhang ZH, Xu HX. Transcriptional regulation of APH-1A and increased gamma-secretase cleavage of APP and Notch by HIF-1 and hypoxia. Faseb J. 2006;20(8):1275.PubMedCrossRef

20.

Gustafsson MV, Zheng X, Pereira T, Gradin K, Jin S, Lundkvist J, Ruas JL, Poellinger L, Lendahl U, Bondesson M. Hypoxia requires notch signaling to maintain the undifferentiated cell state. Dev Cell. 2005;9(5):617–28.PubMedCrossRef

21.

Liu Z, Li C, Meng X, Bai Y, Qi J, Wang J, Zhou Q, Zhang W, Zhang X. Hypoxia-inducible factor-lalpha mediates aggrecan and collagen pi expression via NOTCH1 signaling in nucleus pulposus cells during intervertebral disc degeneration. Biochem Biophys Res Commun. 2017;488(3):554–61.PubMedCrossRef

22.

Xiao L, Ni CL, Shi JD, Wang ZR, Wang SC, Zhang JW, Lu AQ. Analysis of correlation between vertebral endplate change and lumbar disc degeneration. Med Sci Monitor. 2017;23:4932–8.CrossRef

23.

Burke JG, Watson RWG, McCormack D, Dowling FE, Walsh MG, Fitzpatrick JM. Intervertebral discs which cause low back pain secrete high levels of proinflammatory mediators. J Bone Joint Surg-Br Vol. 2002;84B(2):196–201.CrossRef

24.

Risbud MV, Shapiro IM. Role of cytokines in intervertebral disc degeneration: pain and disc content. Nat Rev Rheumatol. 2014;10(1):44–56.PubMedCrossRef

25.

Zheng YX, Liu CC, Ni L, Liu ZY, Mirando AJ, Lin J, Saijilafu, Chen D, Hilton MJ, Li B, et al. Cell type-specific effects of notch signaling activation on intervertebral discs: Implications for intervertebral disc degeneration. J Cell Physiol. 2018;233(7):5431–40.PubMedPubMedCentralCrossRef

26.

Kwon WK, Moon HJ, Kwon TH, Park YK, Kim JH. The role of hypoxia in angiogenesis and extracellular matrix regulation of intervertebral disc cells during inflammatory reactions. Neurosurgery. 2017;81(5):867–75.PubMed

27.

Capoor MN, Ruzicka F, Machackova T, Jancalek R, Smrcka M, Schmitz JE, Hermanova M, Sana J, Michu E, Baird JC et al: Prevalence of Propionibacterium acnes in Intervertebral Discs of Patients Undergoing Lumbar Microdiscectomy: A Prospective Cross-Sectional Study. PLoS One. 2016;11(8):e0161676.

28.

Stirling A, Worthington T, Rafiq M, Lambert PA, Elliott TSJ. Association between sciatica and Propionibacterium acnes. Lancet. 2001;357(9273):2024–5.PubMedCrossRef

29.

Yuan Y, Chen Y, Zhou Z, Jiao Y, Li C, Zheng Y, Lin Y, Xiao J, Chen Z, Cao P. Association between chronic inflammation and latent infection of Propionibacterium acnes in non-pyogenic degenerated intervertebral discs: a pilot study. Eur Spine J. 2018;27(10):2506–17.PubMedCrossRef

30.

Ohtori S, Inoue G, Ito T, Koshi T, Ozawa T, Doya H, Saito T, Moriya H, Takahashi K. Tumor necrosis factor-immunoreactive cells and PGP 9.5-immunoreactive nerve fibers in vertebral endplates of patients with discogenic low back pain and Modic type 1 or type 2 changes on MRI. Spine. 2006;31(9):1026–31.PubMedCrossRef

Title: Correlation between the HIF-1α/Notch signaling pathway and Modic changes in nucleus pulposus cells isolated from patients with low back pain
Authors: Zekang Xiong
Jun Ding
Jinge Zhou
Sheng Yao
Jin Zheng
Xiaodong Guo
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Back Pain
Back Pain
Back Pain
Published in: BMC Musculoskeletal Disorders / Issue 1/2020
Electronic ISSN: 1471-2474
DOI: https://doi.org/10.1186/s12891-020-03505-w

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Correlation between the HIF-1α/Notch signaling pathway and Modic changes in nucleus pulposus cells isolated from patients with low back pain

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2020

Effects of delayed hip replacement on postoperative hip function and quality of life in elderly patients with femoral neck fracture

Joint motion of bipolar hemiarthroplasty in routine hip functional movements: a dynamic motion study

Women’s experiences of the journey to chronic widespread pain: a qualitative study

Unstable intertrochanteric fractures are associated with a greater hemoglobin drop during the perioperative period: a retrospective case control study

Association of Modic change types and their short tau inversion recovery signals with clinical characteristics- a cross sectional study of chronic low back pain patients in the AIM-study

The method for measurement of the three-dimensional scoliosis angle from standard radiographs