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Is bone density associated with intervertebral disc pressure in healthy and degenerated discs?

ABSTRACT: The coupling of the intervertebral disc (IVD) and vertebra as a biomechanical unit suggests that changes in the distribution of pressure within the IVD (intradiscal pressure, IDP) as a result of disc degeneration can influence the distribution of bone density within the vertebra, and vice versa. The goal of this study was to assess the correspondence between IDP and bone density in the adjacent vertebrae, with emphasis on how this correspondence differs between healthy and degenerated IVDs. Bone density of the endplates and subchondral bone in regions adjacent to the anterior and posterior annulus fibrosus (aAF and pAF, respectively) and nucleus pulposus (NP) was measured via quantitative computed tomography (QCT) in 61 spine segments (T7-9, T9-11, T10-12; 71±14years). IDP was measured in the aAF, NP, and pAF regions in 26 of the spine segments (68±16years) while they were tested in flexed (5°) or erect postures. Disc degeneration was assessed by multiple grading schemes. No correlation was found between bone density and IDP in either posture (p>0.104). Regional variations in IDP and, to a greater extent bone density, were found to change with advancing degeneration: both IDP (p=0.045) and bone density (p=0.024) decreased in the NP region relative to the aAF region. The finding of only a modest correspondence between degeneration-associated changes in IDP and bone density may arise from complexity in how IDP relates to mechanical force transmission through the endplate and from limitations of the available IVD grading schemes in estimating the mechanical behavior of the IVD.

SUBMITTER: Fein PM

PROVIDER: S-EPMC5699461 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Is bone density associated with intervertebral disc pressure in healthy and degenerated discs?

Fein Paul M PM DelMonaco Alexander A Jackman Timothy M TM Curtiss Cameron C Guermazi Ali A Barest Glenn D GD Morgan Elise F EF

Journal of biomechanics 20170904

The coupling of the intervertebral disc (IVD) and vertebra as a biomechanical unit suggests that changes in the distribution of pressure within the IVD (intradiscal pressure, IDP) as a result of disc degeneration can influence the distribution of bone density within the vertebra, and vice versa. The goal of this study was to assess the correspondence between IDP and bone density in the adjacent vertebrae, with emphasis on how this correspondence differs between healthy and degenerated IVDs. Bone ...[more]

PMID: 28943155

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Project description:IntroductionThe regulation and elevation in expression of the catabolic matrix metalloproteinases (MMPs) is of high importance in the human intervertebral disc since upregulation of these matrix-degrading enzymes results in matrix destruction associated with disc degeneration. MMP28 (epilysin) is a newly discovered MMP believed to play a role in matrix composition and turnover in skin. It is present in basal keratinocytes where its expression is upregulated with wound repair, and in cartilage and synovium where it is upregulated in osteoarthritis. Recent work has shown that mechanical compression can act to modulate expression of MMP28. The expression of MMP28 is unexplored in the intervertebral disc.MethodsFollowing approval by our human subjects institutional review board, we employed microarray analyses to evaluate in vivo expression of MMP28 and the MMP28 precursor in human disc tissue, and utilized immunohistochemistry to determine cellular and extracellular matrix localization of MMP28 in 35 human disc tissue specimens. The percentage of cells positive for MMP28 immunocytochemical localization was also determined.ResultsThe present work documents the expression and presence of MMP28 in cells and extracellular matrix (ECM) of the human intervertebral disc. Gene expression levels in human disc tissue were detectable for both MMP28 and the MMP28 precursor. MMP28 cytoplasmic localization was present in cells of the outer annulus; it was also present in some, but not all, cells of the inner annulus and nucleus. MMP28 was not found in the ECM of healthier Grade I to II discs, but was identified in the ECM of 61% of the more degenerated Grade III to V discs (P = 0.0018). There was a significant difference in cellular MMP28 distribution in the disc (P = 0.008): the outer annulus showed the largest percentage of cells positive for MMP28 immunolocalization, followed by the inner annulus and then the nucleus. Herniated discs showed a significantly greater proportion of MMP28-positive cells compared with nonherniated discs (P = 0.034).ConclusionsFindings presented here show the first documentation of intervertebral disc expression and production of MMP28. MMP28 was found in both disc cell cytoplasm and in the ECM of more degenerated specimens, with greater cellular localization in the outer annulus and in herniated disc specimens. These findings are important because of the key role of MMPs in disc turnover and homeostasis, and previous indications of a role for this MMP in matrix repair and matrix turnover in other tissues. Our data, which show the presence of MMP28 in human disc tissue, suggest that MMP28 may have a potentially important role in ECM modulation in the healthy and degenerating disc.

Project description:The distribution of bone tissue within the vertebra can modulate vertebral strength independently of average density and may change with age and disc degeneration. Our results show that the age-associated decrease in bone density is spatially non-uniform and associated with disc health, suggesting a mechanistic interplay between disc and vertebra. PURPOSE:While the decline of bone mineral density (BMD) in the aging spine is well established, the extent to which age influences BMD distribution within the vertebra is less clear. Measures of regional BMD (rBMD) may improve predictions of vertebral strength and suggest how vertebrae might adapt with intervertebral disc degeneration. Thus, we aimed to assess how rBMD values were associated with age, sex, and disc height loss (DHL). METHODS:We measured rBMD in the L3 vertebra of 377 participants from the Framingham Heart Study (41-83 years, 181 M/196 F). Integral (Int.BMD) and trabecular BMD (Tb.BMD) were measured from QCT images. rBMD ratios (anterior/posterior, superior/mid-transverse, inferior/mid-transverse, and central/outer) were calculated from the centrum. A radiologist assigned a DHL severity score to adjacent intervertebral discs (L2-L3 and L3-L4). RESULTS:Int.BMD and Tb.BMD were both associated with age, though the decrease across age was greater in women (Int.BMD, -?2.6 mg/cm3 per year; Tb.BMD, -?2.6 mg/cm3 per year) than men (Int.BMD, -?0.5 mg/cm3 per year; Tb.BMD, -?1.2 mg/cm3 per year). The central/outer (-?0.027/decade) and superior/mid-transverse (-?0.018/decade) rBMD ratios were negatively associated with age, with similar trends in men and women. Higher Int.BMD or Tb.BMD was associated with increased odds of DHL after adjusting for age and sex. Low central/outer ratio and high anterior/poster and superior/mid-transverse ratios were also associated with increased odds of DHL. CONCLUSIONS:Our results indicate that the distribution of bone within the L3 vertebra is different across age, but not between sexes, and is associated with disc degeneration.

Project description:Intervertebral disc (IVD) degeneration is a pathological process, which may lead to lower back pain. The present study aimed to investigate the pathogenesis of IVD degeneration. GSE42611 was downloaded from Gene Expression Omnibus, including 4 nucleus pulposus samples isolated from degenerated IVDs and 4 nucleus pulposus samples separated from normal IVDs. The differentially expressed genes (DEGs) between the degenerated and normal samples were screened using the limma package in R. Functional and pathway enrichment analyses were conducted separately for the upregulated and downregulated genes, using Database for Annotation, Visualization and Integrated Discovery software. In addition, protein‑protein interaction (PPI) networks were constructed using the Search Tool for the Retrieval of Interacting Genes database and Cytoscape software. Finally, module analyses were conducted for the PPI networks using the MCODE plug‑in in Cytoscape. A total of 558 DEGs were identified in the degenerated nucleus pulposus cells: 253 upregulated and 305 downregulated. Pathway enrichment analysis revealed that downregulated thrombospondin 1 (THBS1) was enriched in extracellular matrix‑receptor interaction. Interleukin (IL)‑6 in the PPI network for the upregulated genes and vascular endothelial growth factor A (VEGFA) in the PPI network for the downregulated genes had higher degrees. Additionally, four modules (µM1, µM2, µM3 and µM4) were identified from the PPI network for the upregulated genes. Four modules (dM1, dM2, dM3 and dM4) were identified from the PPI network for the downregulated genes. In the dM2 module, collagen genes and integrin subunit α4 (ITGA4) may interact with each other. Additionally, functional enrichment indicated that collagen genes were enriched in extracellular matrix organization. In conclusion, IL‑6, VEGFA, THBS1, ITGA4 and collagen genes may contribute to the progression of IVD degeneration. These results suggested that the manipulation of these genes and their products may have potential as a novel therapeutic strategy for the treatment of patients with IVD.

Dataset Information

Is bone density associated with intervertebral disc pressure in healthy and degenerated discs?

Publications

Is bone density associated with intervertebral disc pressure in healthy and degenerated discs?

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