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Molecular interactions between human cartilaginous endplates and nucleus pulposus cells: a preliminary investigation.

Abstract：

STUDY DESIGN:Conditioned media (CM) of cartilaginous endplates (CEPs) of intervertebral discs were analyzed in a bioassay with regard to their influence on matrix turnover and inflammatory factors on nucleus pulposus (NP) cells of the same patient. CEP tissue underwent further histological and ultrastructural analysis. OBJECTIVE:To identify possible interactions between the CEP and the disc via molecular factors that may influence disc matrix degradation and to determine degenerative changes of CEP tissue. SUMMARY OF BACKGROUND DATA:Impaired endplate perme-ability due to degeneration and calcification is considered to be a key contributor to disc degeneration. An upregulation of metalloproteinases and inflammatory cytokines has been observed in degenerated intervertebral discs. Possibly, the CEP contributes to the regulation of disc matrix degradation via molecular interactions with the disc tissue. METHODS:CEP and NP cells from the same patients (n = 6) were investigated in a bioassay with regard to their influence on matrix turnover and inflammatory factors. We determined gene expression of NP cells in alginate beads that were exposed to CM of CEP punches (CEP-CM) from the same patients. The CEP-CMs were analyzed by protein array for inflammatory cytokines. Further CEP samples underwent histological (n = 15) and ultrastructural analysis (n = 8) to determine alterations of cell and matrix structure. RESULTS:NP cells exposed to their donor-corresponding CEP-CM significantly upregulated interleukins (IL-6, IL-8) and matrix metalloproteinase (MMP-3, MMP-13) expression, and significantly decreased aggrecan and collagen type 2 expression. Proinflammatory cytokines were identified in the CEP-CM. The occurrence of apoptotic cells and degraded matrix fragments varied strongly between donors. CONCLUSION:Our results indicate interactions between the CEP and the NP tissue via molecular factors that upregulate matrix degrading enzymes and inflammatory cytokines and thereby influence the pathophysiology of disc degeneration. Ongoing investigations will further identify the regulative role of potential molecular factors that are responsible for these degenerative alterations. LEVEL OF EVIDENCE:N/A.

journal_name

Spine (Phila Pa 1976)

journal_title

Spine

authors

Neidlinger-Wilke C,Boldt A,Brochhausen C,Galbusera F,Carstens C,Copf F,Schultheiss M,Lazary A,Brayda-Bruno M,Ignatius A,Wilke HJ

doi

10.1097/BRS.0000000000000372

subject

Has Abstract

pub_date

2014-08-01 00:00:00

pages

1355-64

issue

eissn

0362-2436

issn

1528-1159

journal_volume

pub_type

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Molecular interactions between human cartilaginous endplates and nucleus pulposus cells: a preliminary investigation.