Abstract

The cartilage endplates (CEPs) on the superior and inferior surfaces of the intervertebral disk (IVD), are the primary nutrient transport pathways between the disk and the vertebral body. Passive diffusion is responsible for transporting small nutrient and metabolite molecules through the avascular CEPs. The baseline solute diffusivities in healthy CEPs have been previously studied, however alterations in CEP diffusion associated with IVD degeneration remain unclear. This study aimed to quantitatively compare the solute diffusion in healthy and degenerated human CEPs using a fluorescence recovery after photobleaching (FRAP) approach. Seven healthy CEPs and 22 degenerated CEPs were collected from five fresh-frozen human cadaveric spines and 17 patients undergoing spine fusion surgery, respectively. The sodium fluorescein diffusivities in CEP radial and vertical directions were measured using the FRAP method. The CEP calcification level was evaluated by measuring the average X-ray attenuation. No difference was found in solute diffusivities between radial and axial directions in healthy and degenerated CEPs. Compared to healthy CEPs, the average solute diffusivity was 44% lower in degenerated CEPs (Healthy: 29.07 μm2/s (CI: 23.96–33.62 μm2/s); degenerated: 16.32 μm2/s (CI: 13.84–18.84 μm2/s), p < 0.001). The average solute diffusivity had an inverse relationship with the degree of CEP calcification as determined by the normalized X-ray attenuation values (ß = −22.19, R2 = 0.633; p < 0.001). This study suggests that solute diffusion through the disk and vertebral body interface is significantly hindered by CEP calcification, providing clues to help further understand the mechanism of IVD degeneration.

References

1.
Hartvigsen
,
J.
,
Hancock
,
M. J.
,
Kongsted
,
A.
,
Louw
,
Q.
,
Ferreira
,
M. L.
,
Genevay
,
S.
,
Hoy
,
D.
,
Karppinen
,
J.
,
Pransky
,
G.
,
Sieper
,
J.
,
Smeets
,
R. J.
, and
Underwood
,
M.
, and
Lancet Low Back Pain Series Working Group,
2018
, “
What Low Back Pain Is and Why We Need to Pay Attention
,”
Lancet
,
391
(
10137
), pp.
2356
2367
.10.1016/S0140-6736(18)30480-X
2.
Luoma
,
K.
,
Riihimaki
,
H.
,
Luukkonen
,
R.
,
Raininko
,
R.
,
Viikari-Juntura
,
E.
, and
Lamminen
,
A.
,
2000
, “
Low Back Pain in Relation to Lumbar Disc Degeneration
,”
Spine
,
25
(
4
), pp.
487
492
.10.1097/00007632-200002150-00016
3.
Munir
,
S.
,
Freidin
,
M. B.
,
Rade
,
M.
,
Maatta
,
J.
,
Livshits
,
G.
, and
Williams
,
F. M. K.
,
2018
, “
Endplate Defect Is Heritable, Associated With Low Back Pain and Triggers Intervertebral Disc Degeneration: A Longitudinal Study From TwinsUK
,”
Spine
,
43
(
21
), pp.
1496
1501
.10.1097/BRS.0000000000002721
4.
Vlaeyen
,
J. W. S.
,
Maher
,
C. G.
,
Wiech
,
K.
,
Van Zundert
,
J.
,
Meloto
,
C. B.
,
Diatchenko
,
L.
,
Battié
,
M. C.
,
Goossens
,
M.
,
Koes
,
B.
, and
Linton
,
S. J.
,
2018
, “
Low Back Pain
,”
Nat. Rev. Dis. Primers
,
4
(
1
), p.
52
.10.1038/s41572-018-0052-1
5.
Maroudas
,
A.
,
Stockwell
,
R. A.
,
Nachemson
,
A.
, and
Urban
,
J.
,
1975
, “
Factors Involved in the Nutrition of the Human Lumbar Intervertebral Disc: Cellularity and Diffusion of Glucose In Vitro
,”
J. Anat.
,
120
(
Pt 1
), pp.
113
130
.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1231728/
6.
Wong
,
J.
,
Sampson
,
S.
,
Bell-Briones
,
H.
,
Ouyang
,
A.
,
Lazar
,
A.
,
Lotz
,
J.
, and
Fields
,
A.
,
2019
, “
Nutrient Supply and Nucleus Pulposus Cell Function: Effects of the Transport Properties of the Cartilage Endplate and Potential Implications for Intradiscal Biologic Therapy
,”
Osteoarthritis Cartilage
,
27
(
6
), pp.
956
964
.10.1016/j.joca.2019.01.013
7.
Ogata
,
K.
, and
Whiteside
,
L. A.
,
1981
, “
Nutritional Pathways of the Intervertebral Disc: An Experimental Study Using Hydrogen Washout Technique
,”
Spine
,
6
(
3
), pp.
211
216
.10.1097/00007632-198105000-00003
8.
Wu
,
Y.
,
Cisewski
,
S. E.
,
Wegner
,
N.
,
Zhao
,
S.
,
Pellegrini
,
V. D.
, Jr.
,
Slate
,
E. H.
, and
Yao
,
H.
,
2016
, “
Region and Strain-Dependent Diffusivities of Glucose and Lactate in Healthy Human Cartilage Endplate
,”
J. Biomech.
,
49
(
13
), pp.
2756
2762
.10.1016/j.jbiomech.2016.06.008
9.
Wu
,
Y.
,
Cisewski
,
S. E.
,
Sun
,
Y.
,
Damon
,
B. J.
,
Sachs
,
B. L.
,
Pellegrini
,
V. D.
, Jr.
,
Slate
,
E. H.
, and
Yao
,
H.
,
2017
, “
Quantifying Baseline Fixed Charge Density in Healthy Human Cartilage Endplate: A Two-Point Electrical Conductivity Method
,”
Spine
,
42
(
17
), pp.
E1002
E1009
.10.1097/BRS.0000000000002061
10.
DeLucca
,
J. F.
,
Cortes
,
D. H.
,
Jacobs
,
N. T.
,
Vresilovic
,
E. J.
,
Duncan
,
R. L.
, and
Elliott
,
D. M.
,
2016
, “
Human Cartilage Endplate Permeability Varies With Degeneration and Intervertebral Disc Site
,”
J. Biomech.
,
49
(
4
), pp.
550
557
.10.1016/j.jbiomech.2016.01.007
11.
Fields
,
A. J.
,
Rodriguez
,
D.
,
Gary
,
K. N.
,
Liebenberg
,
E. C.
, and
Lotz
,
J. C.
,
2014
, “
Influence of Biochemical Composition on Endplate Cartilage Tensile Properties in the Human Lumbar Spine
,”
J. Orthop. Res.
,
32
(
2
), pp.
245
252
.10.1002/jor.22516
12.
Wu
,
Y.
,
Cisewski
,
S.
,
Sachs
,
B. L.
, and
Yao
,
H.
,
2013
, “
Effect of Cartilage Endplate on Cell Based Disc Regeneration: A Finite Element Analysis
,”
Mol. Cell. Biomech.
,
10
(
2
), pp.
159
182
.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4315260/
13.
Huang
,
Y. C.
,
Urban
,
J. P.
, and
Luk
,
K. D.
,
2014
, “
Intervertebral Disc Regeneration: Do Nutrients Lead the Way?
,”
Nat. Rev. Rheumatol.
,
10
(
9
), pp.
561
566
.10.1038/nrrheum.2014.91
14.
Urban
,
J.
,
Holm
,
S.
,
Maroudas
,
A.
, and
Nachemson
,
A.
,
1982
, “
Nutrition of the Intervertebral Disc: Effect of Fluid Flow on Solute Transport
,”
Clin. Orthop. Relat. Res.
, 170, pp.
296
302
.10.1097/00003086-198210000-00039
15.
Jackson
,
A. R.
,
Huang
,
C.-Y. C.
,
Brown
,
M. D.
, and
Gu
,
W. Y.
,
2011
, “
3D Finite Element Analysis of Nutrient Distributions and Cell Viability in the Intervertebral Disc: Effects of Deformation and Degeneration
,”
ASME J. Biomech. Eng.
,
133
(
9
), p.
01006
.10.1115/1.4004944
16.
Nachemson
,
A.
,
Lewin
,
T.
,
Maroudas
,
A.
, and
Freeman
,
M.
,
1970
, “
In Vitro Diffusion of Dye Through the End-Plates and the Annulus Fibrosus of Human Lumbar Inter-Vertebral Discs
,”
Acta Orthop. Scand.
,
41
(
6
), pp.
589
607
.10.3109/17453677008991550
17.
Rajasekaran
,
S.
,
Babu
,
J. N.
,
Arun
,
R.
,
Armstrong
,
B. R.
,
Shetty
,
A. P.
, and
Murugan
,
S.
,
2004
, “
A Study of Diffusion in Human Lumbar Discs: A Serial Magnetic Resonance Imaging Study Documenting the Influence of the Endplate on Diffusion in Normal and Degenerate Discs
,”
Spine
,
29
(
23
), pp.
2654
2667
.10.1097/01.brs.0000148014.15210.64
18.
Roberts
,
S.
,
Menage
,
J.
, and
Eisenstein
,
S.
,
1993
, “
The Cartilage Endplate and Intervertebral Disc in Scoliosis: Calcification and Other Sequelae
,”
J. Orthop. Res.
,
11
(
5
), pp.
747
757
.10.1002/jor.1100110517
19.
Dolor
,
A.
,
Sampson
,
S. L.
,
Lazar
,
A. A.
,
Lotz
,
J. C.
,
Szoka
,
F. C.
, and
Fields
,
A. J.
,
2019
, “
Matrix Modification for Enhancing the Transport Properties of the Human Cartilage Endplate to Improve Disc Nutrition
,”
PLoS One
,
14
(
4
), p.
e0215218
.10.1371/journal.pone.0215218
20.
Grant
,
M. P.
,
Epure
,
L. M.
,
Bokhari
,
R.
,
Roughley
,
P.
,
Antoniou
,
J.
, and
Mwale
,
F.
,
2016
, “
Human Cartilaginous Endplate Degeneration Is Induced by Calcium and the Extracellular Calcium-Sensing Receptor in the Intervertebral Disc
,”
Eur. Cells Mater.
,
32
, pp.
137
151
.10.22203/eCM.v032a09
21.
Urban
,
J.
,
Holm
,
S.
, and
Maroudas
,
A.
,
1978
, “
Diffusion of Small Solutes Into the Intervertebral Disc: As In Vitro Study
,”
Biorheology
,
15
(
3–4
), pp.
203
223
.10.3233/BIR-1978-153-409
22.
Travascio
,
F.
,
Jackson
,
A. R.
,
Brown
,
M. D.
, and
Gu
,
W. Y.
,
2009
, “
Relationship Between Solute Transport Properties and Tissue Morphology in Human Annulus Fibrosus
,”
J. Orthop. Res.
,
27
(
12
), pp.
1625
1630
.10.1002/jor.20927
23.
Shi
,
C.
,
Wright
,
G. J.
,
Ex-Lubeskie
,
C. L.
,
Bradshaw
,
A. D.
, and
Yao
,
H.
,
2013
, “
Relationship Between Anisotropic Diffusion Properties and Tissue Morphology in Porcine TMJ Disc
,”
Osteoarthritis Cartilage
,
21
(
4
), pp.
625
633
.10.1016/j.joca.2013.01.010
24.
Wu
,
Y.
,
Cisewski
,
S. E.
,
Sachs
,
B. L.
,
Pellegrini
,
V. D.
, Jr.
,
Kern
,
M. J.
,
Slate
,
E. H.
, and
Yao
,
H.
,
2015
, “
The Region-Dependent Biomechanical and Biochemical Properties of Bovine Cartilaginous Endplate
,”
J. Biomech.
,
48
(
12
), pp.
3185
3191
.10.1016/j.jbiomech.2015.07.005
25.
Jackson
,
A. R.
,
Travascio
,
F.
, and
Gu
,
W. Y.
,
2009
, “
Effect of Mechanical Loading on Electrical Conductivity in Human Intervertebral Disk
,”
ASME J. Biomech. Eng.
,
131
(
5
), p.
054505
.10.1115/1.3116152
26.
Jackson
,
A. R.
,
Yuan
,
T. Y.
,
Huang
,
C. Y.
,
Travascio
,
F.
, and
Yong Gu
,
W.
,
2008
, “
Effect of Compression and Anisotropy on the Diffusion of Glucose in Annulus Fibrosus
,”
Spine
,
33
(
1
), pp.
1
7
.10.1097/BRS.0b013e31815e4136
27.
Maroudas
,
A.
,
1970
, “
Distribution and Diffusion of Solutes in Articular Cartilage
,”
Biophys. J.
,
10
(
5
), pp.
365
379
.10.1016/S0006-3495(70)86307-X
28.
Shi
,
C.
,
Kuo
,
J.
,
Bell
,
P. D.
, and
Yao
,
H.
,
2010
, “
Anisotropic Solute Diffusion Tensor in Porcine TMJ Discs Measured by FRAP With Spatial Fourier Analysis
,”
Ann. Biomed. Eng.
,
38
(
11
), pp.
3398
3408
.10.1007/s10439-010-0099-y
29.
Chen
,
P.
,
Chen
,
X.
,
Hepfer
,
R. G.
,
Damon
,
B. J.
,
Shi
,
C.
,
Yao
,
J. J.
,
Coombs
,
M. C.
,
Kern
,
M. J.
,
Ye
,
T.
, and
Yao
,
H.
,
2021
, “
A Noninvasive Fluorescence Imaging-Based Platform Measures 3D Anisotropic Extracellular Diffusion
,”
Nat. Commun.
,
12
(
1
), p.
1913
.10.1038/s41467-021-22221-0
30.
Thompson
,
J. P.
,
Pearce
,
R. H.
,
Schechter
,
M. T.
,
Adams
,
M. E.
,
Tsang
,
I. K.
, and
Bishop
,
P. B.
,
1990
, “
Preliminary Evaluation of a Scheme for Grading the Gross Morphology of the Human Intervertebral Disc
,”
Spine
,
15
(
5
), pp.
411
415
.10.1097/00007632-199005000-00012
31.
Roberts
,
S.
,
Urban
,
J. P.
,
Evans
,
H.
, and
Eisenstein
,
S. M.
,
1996
, “
Transport Properties of the Human Cartilage Endplate in Relation to Its Composition and Calcification
,”
Spine
,
21
(
4
), pp.
415
420
.10.1097/00007632-199602150-00003
32.
Spillekom
,
S.
,
Smolders
,
L. A.
,
Grinwis
,
G. C.
,
Arkesteijn
,
I. T.
,
Ito
,
K.
,
Meij
,
B. P.
, and
Tryfonidou
,
M. A.
,
2014
, “
Increased Osmolarity and Cell Clustering Preserve Canine Notochordal Cell Phenotype in Culture
,”
Tissue Eng., Part C
,
20
(
8
), pp.
652
662
.10.1089/ten.tec.2013.0479
33.
Travascio
,
F.
,
Valladares-Prieto
,
S.
, and
Jackson
,
A. R.
,
2020
, “
Effects of Solute Size and Tissue Composition on Molecular and Macromolecular Diffusivity in Human Knee Cartilage
,”
Osteoarthritis Cartilage Open
,
2
(
4
), p.
100087
.10.1016/j.ocarto.2020.100087
34.
Travascio
,
F.
,
Devaux
,
F.
,
Volz
,
M.
, and
Jackson
,
A. R.
,
2020
, “
Molecular and Macromolecular Diffusion in Human Meniscus: Relationships With Tissue Structure and Composition
,”
Osteoarthritis Cartilage
,
28
(
3
), pp.
375
382
.10.1016/j.joca.2019.12.006
35.
Schwartz
,
G.
,
Morejon
,
A.
,
Best
,
T. M.
,
Jackson
,
A. R.
, and
Travascio
,
F.
,
2022
, “
Strain-Dependent Diffusivity of Small and Large Molecules in Meniscus
,”
ASME J. Biomech. Eng.
,
144
(
11
), p.
111010
.10.1115/1.4054931
36.
Burstein
,
D.
,
Gray
,
M. L.
,
Hartman
,
A. L.
,
Gipe
,
R.
, and
Foy
,
B. D.
,
1993
, “
Diffusion of Small Solutes in Cartilage as Measured by Nuclear Magnetic Resonance (NMR) Spectroscopy and Imaging
,”
J. Orthop. Res.
,
11
(
4
), pp.
465
478
.10.1002/jor.1100110402
37.
Gu
,
W. Y.
,
Yao
,
H.
,
Huang
,
C. Y.
, and
Cheung
,
H. S.
,
2003
, “
New Insight Into Deformation-Dependent Hydraulic Permeability of Gels and Cartilage, and Dynamic Behavior of Agarose Gels in Confined Compression
,”
J. Biomech.
,
36
(
4
), pp.
593
598
.10.1016/S0021-9290(02)00437-2
38.
Gu
,
W. Y.
, and
Yao
,
H.
,
2003
, “
Effects of Hydration and Fixed Charge Density on Fluid Transport in Charged Hydrated Soft Tissues
,”
Ann. Biomed. Eng.
,
31
(
10
), pp.
1162
1170
.10.1114/1.1615576
39.
Jackson
,
A. R.
, and
Gu
,
W. Y.
,
2009
, “
Transport Properties of Cartilaginous Tissues
,”
Curr. Rheumatol. Rev.
,
5
(
1
), pp.
40
50
.10.2174/157339709787315320
40.
Shirazi-Adl
,
A.
,
Taheri
,
M.
, and
Urban
,
J. P.
,
2010
, “
Analysis of Cell Viability in Intervertebral Disc: Effect of Endplate Permeability on Cell Population
,”
J. Biomech.
,
43
(
7
), pp.
1330
1336
.10.1016/j.jbiomech.2010.01.023
41.
Soukane
,
D. M.
,
Shirazi-Adl
,
A.
, and
Urban
,
J. P.
,
2007
, “
Computation of Coupled Diffusion of Oxygen, Glucose and Lactic Acid in an Intervertebral Disc
,”
J. Biomech.
,
40
(
12
), pp.
2645
2654
.10.1016/j.jbiomech.2007.01.003
42.
Huang
,
C. Y.
, and
Gu
,
W. Y.
,
2008
, “
Effects of Mechanical Compression on Metabolism and Distribution of Oxygen and Lactate in Intervertebral Disc
,”
J. Biomech.
,
41
(
6
), pp.
1184
1196
.10.1016/j.jbiomech.2008.02.002
43.
Gu
,
W. Y.
,
Mao
,
X. G.
,
Rawlins
,
B. A.
,
Iatridis
,
J. C.
,
Foster
,
R. J.
,
Sun
,
D. N.
,
Weidenbaum
,
M.
, and
Mow
,
V. C.
,
1999
, “
Streaming Potential of Human Lumbar Anulus Fibrosus Is Anisotropic and Affected by Disc Degeneration
,”
J. Biomech.
,
32
(
11
), pp.
1177
1182
.10.1016/S0021-9290(99)00118-9
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