Dataset Information

Is remaining intervertebral disc tissue interfering with bone generation during fusion of two vertebrae?

ABSTRACT:

Study design

laboratory research.

Background

Through the increasing number of minimally invasive procedures in spinal fusion surgery, the complete removal of intervertebral disc (IVD) tissue has become more a challenge. Remaining IVD may interfere with the biological process of bone formation.

Objective

In order to establish whether complete removal of IVD tissue will improve or inhibit the fusion process, the effects of different concentrations of extracts of inflamed disc tissue on the mitochondrial activity of mesenchymal stem cells (MSCs), and the capacity to mineralize their extracellular matrix by osteoblasts and differentiated MSCs were tested in vitro.

Methods

A MTT assay was conducted to measure the mitochondrial activity of MSCs, and an Alizarin Red S staining quantification assay to measure the deposition of calcium by osteoblasts and differentiated, bone marrow-derived MSCs.

Results

A significantly higher mitochondrial activity was shown in MSCs co-cultured with extracts of IVD tissue (10%, 50%, and 100%) compared with the control group after 48 hours of incubation, indicating that the IVD tissue extracts stimulated the mitochondrial activity of MSCs. This effect appeared to be inversely proportional to the concentration of IVD tissue extract. No significant differences in mineralization by human osteoblasts or differentiated MSCs were found between the samples incubated with IVD tissue extracts (3% and 33%) and the control samples.

Conclusion

Our findings indicate that remaining IVD tissue has more of a stimulating than inhibiting effect on the activity of MSCs. Even if inflammatory cytokines are produced, these do not result in a net inhibition of cellular activity or osteogenic differentiation of MSCs.

SUBMITTER: Kok D

PROVIDER: S-EPMC6483188 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Is remaining intervertebral disc tissue interfering with bone generation during fusion of two vertebrae?

Kok D D Peeters C M M CMM Mardina Z Z Oterdoom D L M DLM Bulstra S K SK Veldhuizen A G AG Kuijer R R Wapstra F H FH

PloS one 20190425 4

<h4>Study design</h4>laboratory research.<h4>Background</h4>Through the increasing number of minimally invasive procedures in spinal fusion surgery, the complete removal of intervertebral disc (IVD) tissue has become more a challenge. Remaining IVD may interfere with the biological process of bone formation.<h4>Objective</h4>In order to establish whether complete removal of IVD tissue will improve or inhibit the fusion process, the effects of different concentrations of extracts of inflamed disc ...[more]

PMID: 31022268

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Project description:Very little is known about how intervertebral disc (IVD) is formed or maintained. Members of the TGF-ß superfamily are secreted signaling proteins that regulate many aspects of development including cellular differentiation. We recently showed that deletion of Tgfbr2 in Col2a expressing tissue results in alterations in development of IVD annulus fibrosus. The results suggested TGF-ß has an important role in regulating development of the axial skeleton, however, the mechanistic basis of TGF-ß action in these specialized joints is not known. One of the hurdles to understanding development of IVD is a lack of known markers. To identify genes that are enriched in the developing IVD and to begin to understand the mechanism of TGF-ß action in IVD development, we undertook a global analysis of gene expression comparing gene expression profiles in developing vertebrae and IVD. We also compared expression profiles in tissues from wild type and Tgfbr2 mutant mice. Lists of IVD and vertebrae enriched genes were generated. Expression patterns for several genes were verified either through in situ hybridization or literature/ database searches resulting in a list of genes that can be used as markers of IVD. Cluster analysis using genes listed under the Gene Ontology terms multicellular organism development and pattern specification indicated that mutant IVD more closely resembled vertebrae than wild type IVD. We propose TGF-ß has two functions in IVD development: 1) to prevent chondrocyte differentiation in the presumptive IVD and 2) to promote differentiation of annulus fibrosus from sclerotome. We have identified genes that are enriched in the IVD and regulated by TGF-ß that warrant further investigation as regulators of IVD development. Thirteen samples were analyzed. This includes three biological replicates of laser captured IVD from E13.5 day control mice, three biological replicates of laser captured vertebrae from the same E13.5 day control mice, three biological relicates of laser captured vertebrae from E13.5 day Col2aCre;Tgfbr2lox/lox mice, and four biological replicates of laser captured IVD from E13.5 day Col2aCre;Tgfbr2lox/lox mice.

Project description:BackgroundRecently we proposed an evolutionary explanation for a spinal pathology that afflicts many people, intervertebral disc herniation (Plomp et al. [2015] BMC Evolutionary Biology 15, 68). Using 2D data, we found that the bodies and pedicles of lower vertebrae of pathological humans were more similar in shape to those of chimpanzees than were those of healthy humans. Based on this, we hypothesized that some individuals are more prone to intervertebral disc herniation because their vertebrae exhibit ancestral traits and therefore are less well adapted for the stresses associated with bipedalism. Here, we report a study in which we tested this "Ancestral Shape Hypothesis" with 3D data from the last two thoracic and first lumbar vertebrae of pathological Homo sapiens, healthy H. sapiens, Pan troglodytes, and several extinct hominins.ResultsWe found that the pathological and healthy H. sapiens vertebrae differed significantly in shape, and that the pathological H. sapiens vertebrae were closer in shape to the P. troglodytes vertebrae than were the healthy H. sapiens vertebrae. Additionally, we found that the pathological human vertebrae were generally more similar in shape to the vertebrae of the extinct hominins than were the healthy H. sapiens vertebrae. These results are consistent with the predictions of the Ancestral Shape Hypothesis. Several vertebral traits were associated with disc herniation, including a vertebral body that is both more circular and more ventrally wedged, relatively short pedicles and laminae, relatively long, more cranio-laterally projecting transverse processes, and relatively long, cranially-oriented spinous processes. We found that there are biomechanical and comparative anatomical reasons for suspecting that all of these traits are capable of predisposing individuals to intervertebral disc herniation.ConclusionsThe results of the present study add weight to the hypothesis that intervertebral disc herniation in H. sapiens is connected with vertebral shape. Specifically, they suggest that individuals whose vertebrae are towards the ancestral end of the range of shape variation within H. sapiens have a greater propensity to develop the condition than other individuals. More generally, the study shows that evolutionary thinking has the potential to shed new light on human skeletal pathologies.

Dataset Information

Is remaining intervertebral disc tissue interfering with bone generation during fusion of two vertebrae?

Study design

Background

Objective

Methods

Results

Conclusion

Publications

Is remaining intervertebral disc tissue interfering with bone generation during fusion of two vertebrae?

Similar Datasets

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