age-related changes in human cervical, thoracal and lumbar intervertebral disc exhibit a strong...

365Journal Reports / The Spine Journal 13 (2013) 363–365

mice elicited a similar reduction in PG. These data demonstrate that gen-

otoxic stress drives degenerative changes associated with IDD.

Published by Elsevier Ireland Ltd.

PMID: 23262094 [PubMed - in process. Available at: http://www.ncbi.

nlm.nih.gov/pubmed/23262094].

Reprinted from: Nasto LA, Wang D, Robinson AR, et al. Genotoxic stress

accelerates age-associated degenerative changes in intervertebral discs.

Mech Ageing Dev 2013;134(1–2):35–42. Epub 2012 Dec 19, with permis-

sion from Elsevier.

http://dx.doi.org/10.1016/j.spinee.2013.02.024

Exhaustion of nucleus pulposus progenitor cells with ageing and

degeneration of the intervertebral disc. Sakai D, Nakamura Y, Nakai

T, et al. Nat Commun 2012;3:1264.

Despite the high prevalence of intervertebral disc disease, little is known

about changes in intervertebral disc cells and their regenerative potential

with ageing and intervertebral disc degeneration. Here we identify popula-

tions of progenitor cells that are Tie2 positive (Tie2(þ)) and disialogan-

glioside 2 positive (GD2(þ)), in the nucleus pulposus from mice and

humans. These cells form spheroid colonies that express type II collagen

and aggrecan. They are clonally multipotent and differentiated into mesen-

chymal lineages and induced reorganization of nucleus pulposus tissue

when transplanted into non-obese diabetic/severe combined immunodefi-

cient mice. The frequency of Tie2(þ) cells in tissues from patients de-

creases markedly with age and degeneration of the intervertebral disc,

suggesting exhaustion of their capacity for regeneration. However, progen-

itor cells (Tie2(þ)GD2(þ)) can be induced from their precursor cells

(Tie2(þ)GD2(–)) under simple culture conditions. Moreover, angiopoie-

tin-1, a ligand of Tie2, is crucial for the survival of nucleus pulposus cells.

Our results offer insights for regenerative therapy and a new diagnostic

standard.



Sakai D, Nakamura Y, Nakai T, et al. Exhaustion of nucleus pulposus pro-

genitor cells with ageing and degeneration of the intervertebral disc. Nat

Commun 2012;3:1264.


Genetic association studies in lumbar disc degeneration: a systematic

review. Eskola PJ, Lemmel€a S, Kjaer P, et al. PLoS One

2012;7(11):e49995. Epub 2012 Nov 21.

OBJECTIVE: Low back pain is associated with lumbar disc degenera-

tion, which is mainly due to genetic predisposition. The objective of this

study was to perform a systematic review to evaluate genetic association

studies in lumbar disc degeneration as defined on magnetic resonance im-

aging (MRI) in humans.

METHODS: A systematic literature search was conducted in MEDLINE,

MEDLINE In-Process, SCOPUS, ISI Web of Science, The Genetic Asso-

ciation Database and The Human Genome Epidemiology Network for in-

formation published between 1990-2011 addressing genes and lumbar disc

degeneration. Two investigators independently identified studies to deter-

mine inclusion, after which they performed data extraction and analysis.

The level of cumulative genetic association evidence was analyzed accord-

ing to The HuGENet Working Group guidelines.

RESULTS: Fifty-two studies were included for review. Forty-eight studies

reported at least one positive association between a genetic marker and

lumbar disc degeneration. The phenotype definition of lumbar disc degen-

eration was highly variable between the studies and replications were in-

consistent. Most of the associations presented with a weak level of

evidence. The level of evidence was moderate for ASPN (D-repeat),

COL11A1 (rs1676486), GDF5 (rs143383), SKT (rs16924573), THBS2

(rs9406328) and MMP9 (rs17576).

CONCLUSIONS: Based on this first extensive systematic review on the

topic, the credibility of reported genetic associations is mostly weak. Clear

definition of lumbar disc degeneration phenotypes and large population-

based cohorts are needed. An international consortium is needed to stan-

dardize genetic association studies in relation to disc degeneration.



Reprinted from: Eskola PJ, Lemmel€a S, Kjaer P, et al. Genetic associationstudies in lumbar disc degeneration: a systematic review. PLoS One

2012;7(11):e49995. Epub 2012 Nov 21.


Age-related changes in human cervical, thoracal and lumbar

intervertebral disc exhibit a strong intra-individual correlation.

Weiler C, Schietzsch M, Kirchner T, et al. Eur Spine J 2012;21 Suppl

6:S810–8. Epub 2011 Aug 12.

INTRODUCTION: Intervertebral disc (IVD) degeneration is character-

ized as a multifactorial disease, in which the hereditary background is

thought to be of high importance. Accordingly, one would expect all spinal

levels (lumbar/cervical/thoracal) to be affected by above-average disc de-

generation in genetically predisposed individuals. The aim of this study,

therefore, was to analyze the amount of degenerative changes in different

spine levels in humans from different ages.

MATERIALS AND METHODS: In detail, the presence, localization and

abundance of histomorphological changes in the annulus fibrosus (AF) and

nucleus pulposus (NP) in the cervical (C5/C6), thoracic (T2/T3) and lum-

bar (L2/L3) spine were investigated in complete autopsy IVD specimens

(47 individuals) covering a complete age range (0–95 years).

RESULTS: Results indicate that the highest degree of histo-degenerative

changes were observed in the NP in all spine levels and showed an age-re-

lated expression pattern. With regard to the different spine levels, lumbar

disc specimen showed significantly more degenerative changes compared

to cervical and thoracic discs, whereas no statistical difference was ob-

served between cervical and thoracic discs. In summary, highest grades

of degeneration were observed in lumbar discs (especially in the NP). In-

tra-individual correlations between the degeneration score in the different

levels showed a significant individual concordance.

CONCLUSIONS: The intra-individual correlation of degenerative

changes in all three examined spine regions further supports the notion that

individual, i.e. genetic factors are strong predisposing factor for the devel-

opment of age-related disc alterations.



Reprinted with permission from: Weiler C, Schietzsch M, Kirchner T, et al.

Age-related changes in human cervical, thoracal and lumbar intervertebral

disc exhibit a strong intra-individual correlation. Eur Spine J 2012;21

Suppl 6:S810–8. Epub 2011 Aug 12. Available at: http://link.springer.

com/article/10.1007/s00586-011-1922-3


http://www.ncbi.nlm.nih.gov/pubmed/23262094











http://link.springer.com/article/10.1007/s00586-011-1922-3

http://link.springer.com/article/10.1007/s00586-011-1922-3


age-related changes in human cervical, thoracal and lumbar intervertebral disc exhibit a strong...

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