Notochordal and Nucleus Pulposus Marker Expression is Maintained by Sub-populations of Adult Human Nucleus Pulposus Cells Through Aging and Degeneration

Overview

Journal Sci Rep

Specialty Science

Date 2017 May 6

PMID 28473691

Citations 59

Authors

Stephen M Richardson

Francesca E Ludwinski

Kanna K Gnanalingham

Ross A Atkinson

Anthony J Freemont

Judith A Hoyland

Affiliations

Soon will be listed here.

Abstract

The nucleus pulposus (NP) of the intervertebral disc (IVD) demonstrates substantial changes in cell and matrix composition with both ageing and degeneration. While recent transcriptomic profiling studies have helped define human NP cell phenotype, it remains unclear how expression of these markers is influenced by ageing or degeneration. Furthermore, cells of the NP are thought to derive from the notochord, although adult NP lacks identifiable notochordal (NC) cells. This study aimed to confirm expression of previously identified NP and NC marker genes in adult human NP cells from a range of ages and degenerate states. Importantly, using gene expression analysis (N = 60) and immunohistochemistry (N = 56) the study demonstrates expression of NP markers FoxF1, Pax-1, keratin-8/18, carbonic anhydrase-12, and NC markers brachyury, galectin-3 and CD24 in cells of the NP irrespective of age or degeneration. Our immunohistochemical data, combined with flow cytometry (N = 5) which identified a small number of CA12Gal3TCD24 cells, suggests the possible presence of a sub-population of cells with an NC-like phenotype in adult NP tissue. These findings suggest that the NP contains a heterogeneous population of cells, which may possess varied phenotypic and functional profiles and thus warrant further investigation to improve our understanding of IVD homeostasis and repair.

Citing Articles

CD24 Positive Nucleus Pulposus Cells in Adult Human Intervertebral Discs Maintain a More Notochordal Phenotype Than GD2 Positive Cells.

Ionescu A, Baird P, Patel S, Howell G, Hoyland J, Richardson S JOR Spine. 2024; 7(4):e70029.

PMID: 39717383 PMC: 11664240. DOI: 10.1002/jsp2.70029.

Current Therapeutic Strategies of Intervertebral Disc Regenerative Medicine.

Elmounedi N, Bahloul W, Keskes H Mol Diagn Ther. 2024; 28(6):745-775.

PMID: 39158834 DOI: 10.1007/s40291-024-00729-7.

Getting to the Core: Exploring the Embryonic Development from Notochord to Nucleus Pulposus.

Ambrosio L, Schol J, Ruiz-Fernandez C, Tamagawa S, Joyce K, Nomura A J Dev Biol. 2024; 12(3).

PMID: 39051200 PMC: 11270426. DOI: 10.3390/jdb12030018.

Intradiscal Autologous Biologics for the Treatment of Chronic Discogenic Low Back Pain.

Ufondu W, Robinson C, Hussain N, DSouza R, Karri J, Emerick T Curr Pain Headache Rep. 2024; 28(11):1079-1095.

PMID: 39017984 DOI: 10.1007/s11916-024-01294-8.

Single-cell Transcriptomic Studies Unveil Potential Nodes of the Notochord Gene Regulatory Network.

Negron-Pineiro L, Di Gregorio A Integr Comp Biol. 2024; 64(5):1194-1213.

PMID: 38914463 PMC: 11579531. DOI: 10.1093/icb/icae084.

References

Walmsley R . The development and growth of the intervertebral disc. Edinb Med J. 1953; 60(8):341-64. PMC: 5290399. View

Gotz W, Kasper M, Fischer G, Herken R . Intermediate filament typing of the human embryonic and fetal notochord. Cell Tissue Res. 1995; 280(2):455-62. DOI: 10.1007/BF00307819. View

van den Akker G, Surtel D, Cremers A, Richardson S, Hoyland J, van Rhijn L . Novel Immortal Cell Lines Support Cellular Heterogeneity in the Human Annulus Fibrosus. PLoS One. 2016; 11(1):e0144497. PMC: 4721917. DOI: 10.1371/journal.pone.0144497. View

Mercer S, Bogduk N . The ligaments and annulus fibrosus of human adult cervical intervertebral discs. Spine (Phila Pa 1976). 1999; 24(7):619-26; discussion 627-8. DOI: 10.1097/00007632-199904010-00002. View

Oguz E, Tsai T, Di Martino A, Guttapalli A, Albert T, Shapiro I . Galectin-3 expression in the intervertebral disc: a useful marker of the notochord phenotype?. Spine (Phila Pa 1976). 2007; 32(1):9-16. DOI: 10.1097/01.brs.0000250302.74574.98. View

Power K, Grad S, Rutges J, Creemers L, van Rijen M, OGaora P . Identification of cell surface-specific markers to target human nucleus pulposus cells: expression of carbonic anhydrase XII varies with age and degeneration. Arthritis Rheum. 2011; 63(12):3876-86. DOI: 10.1002/art.30607. View

Maniadakis N, Gray A . The economic burden of back pain in the UK. Pain. 1999; 84(1):95-103. DOI: 10.1016/S0304-3959(99)00187-6. View

Sive J, Baird P, Jeziorsk M, Watkins A, Hoyland J, Freemont A . Expression of chondrocyte markers by cells of normal and degenerate intervertebral discs. Mol Pathol. 2002; 55(2):91-7. PMC: 1187156. DOI: 10.1136/mp.55.2.91. View

Minogue B, Richardson S, Zeef L, Freemont A, Hoyland J . Characterization of the human nucleus pulposus cell phenotype and evaluation of novel marker gene expression to define adult stem cell differentiation. Arthritis Rheum. 2010; 62(12):3695-705. DOI: 10.1002/art.27710. View

10.

Gotz W, Kasper M, Miosge N, Hughes R . Detection and distribution of the carbohydrate binding protein galectin-3 in human notochord, intervertebral disc and chordoma. Differentiation. 1998; 62(3):149-57. DOI: 10.1046/j.1432-0436.1997.6230149.x. View

11.

Makela M, Heliovaara M, Sievers K, Impivaara O, Knekt P, Aromaa A . Prevalence, determinants, and consequences of chronic neck pain in Finland. Am J Epidemiol. 1991; 134(11):1356-67. DOI: 10.1093/oxfordjournals.aje.a116038. View

12.

Cappello R, Bird J, Pfeiffer D, Bayliss M, Dudhia J . Notochordal cell produce and assemble extracellular matrix in a distinct manner, which may be responsible for the maintenance of healthy nucleus pulposus. Spine (Phila Pa 1976). 2006; 31(8):873-82. DOI: 10.1097/01.brs.0000209302.00820.fd. View

13.

Matsumoto M, Fujimura Y, Suzuki N, Nishi Y, Nakamura M, Yabe Y . MRI of cervical intervertebral discs in asymptomatic subjects. J Bone Joint Surg Br. 1998; 80(1):19-24. DOI: 10.1302/0301-620x.80b1.7929. View

14.

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

15.

Louman-Gardiner K, Coombe D, Hunter C . Computation models simulating notochordal cell extinction during early ageing of an intervertebral disc. Comput Methods Biomech Biomed Engin. 2011; 14(12):1071-7. DOI: 10.1080/10255842.2010.508037. View

16.

Naka T, Iwamoto Y, Shinohara N, Chuman H, Fukui M, Tsuneyoshi M . Cytokeratin subtyping in chordomas and the fetal notochord: an immunohistochemical analysis of aberrant expression. Mod Pathol. 1997; 10(6):545-51. View

17.

Risbud M, Guttapalli A, Tsai T, Lee J, Danielson K, Vaccaro A . Evidence for skeletal progenitor cells in the degenerate human intervertebral disc. Spine (Phila Pa 1976). 2007; 32(23):2537-44. DOI: 10.1097/BRS.0b013e318158dea6. View

18.

Fujita N, Miyamoto T, Imai J, Hosogane N, Suzuki T, Yagi M . CD24 is expressed specifically in the nucleus pulposus of intervertebral discs. Biochem Biophys Res Commun. 2005; 338(4):1890-6. DOI: 10.1016/j.bbrc.2005.10.166. View

19.

Thorpe A, Binch A, Creemers L, Sammon C, Le Maitre C . Nucleus pulposus phenotypic markers to determine stem cell differentiation: fact or fiction?. Oncotarget. 2016; 7(3):2189-200. PMC: 4823028. DOI: 10.18632/oncotarget.6782. View

20.

Mwale F, Roughley P, Antoniou J . Distinction between the extracellular matrix of the nucleus pulposus and hyaline cartilage: a requisite for tissue engineering of intervertebral disc. Eur Cell Mater. 2004; 8:58-63. DOI: 10.22203/ecm.v008a06. View