Influence of low glucose supply on the regulation of gene expression by nucleus pulposus cells and their responsiveness to mechanical loading

Rinkler, Christina; Heuer, Frank; Pedro, Maria Teresa; Mauer, Uwe Max; Ignatius, Anita; Neidlinger‐Wilke, Cornelia

doi:10.3171/2010.4.spine09713

Cited by 32 publications

(39 citation statements)

References 42 publications

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“…During IVD degeneration, loss of endplate permeability will result in a decrease in the nutrient supply [25]. It is proposed that reduced nutrient levels could be inadequate to maintain cellular viability or activity, leading to IVD degeneration [26-28]. In the present study we found that the reduction in glucose supply slightly reduced cell viability, consistent with previous studies about the influence of low glucose on the viability of NP cells [27,29].…”

Section: Discussionsupporting

confidence: 90%

Responses of human adipose-derived mesenchymal stem cells to chemical microenvironment of the intervertebral disc

Liang

Tao

et al. 2012

J Transl Med

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BackgroundHuman adipose-derived mesenchymal stem cells (ADMSCs) may be ideal source of cells for intervertebral disc (IVD) regeneration, but the harsh chemical microenvironment of IVD may significantly influence the biological and metabolic vitality of ADMSCs and impair their repair potential. This study aimed to investigate the viability, proliferation and the expression of main matrix proteins of ADMSCs in the chemical microenvironment of IVD under normal and degeneration conditions.MethodsADMSCs were harvested from young (aged 8-12 years, n = 6) and mature (aged 33-42 years, n = 6) male donors and cultured under standard condition and IVD-like conditions (low glucose, acidity, high osmolarity, and combined conditions) for 2 weeks. Cell viability was measured by annexin V-FITC and PI staining and cell proliferation was measured by MTT assay. The expression of aggrecan and collagen-I was detected by real-time quantitative polymerase chain reaction and Western blot analysis.ResultsIVD-like glucose condition slightly inhibited cell viability, but increased the expression of aggrecan. In contrast, IVD-like osmolarity, acidity and the combined conditions inhibited cell viability and proliferation and the expression of aggrecan and collagen-I. ADMSCs from young and mature donors exhibited similar responses to the chemical microenvironments of IVD.ConclusionIVD-like low glucose is a positive factor but IVD-like high osmolarity and low pH are deleterious factors that affect the survival and biological behaviors of ADMSCs. These findings may promote the translational research of ADMSCs in IVD regeneration for the treatment of low back pain.

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Section: Discussionsupporting

confidence: 90%

Responses of human adipose-derived mesenchymal stem cells to chemical microenvironment of the intervertebral disc

Liang

Tao

et al. 2012

J Transl Med

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“…When the IVD cells are in a reduced glucose environment, mechanical loading does more harm than good. Under limited glucose supply, axial compression applied on an ovine caudal disc organ culture model [45] or IHP applied on NP cells in alginate beads [100], resulted in elevated MMPs gene expression and/or protein expression. These negative responses were more prominent under hyper-physiological (10 Hz) loading frequency [45].…”

Section: Nutritionmentioning

confidence: 99%

The effects of dynamic loading on the intervertebral disc

2011

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Loading is important to maintain the balance of matrix turnover in the intervertebral disc (IVD). Daily cyclic diurnal assists in the transport of large soluble factors across the IVD and its surrounding circulation and applies direct and indirect stimulus to disc cells. Acute mechanical injury and accumulated overloading, however, could induce disc degeneration. Recently, there is more information available on how cyclic loading, especially axial compression and hydrostatic pressure, affects IVD cell biology. This review summarises recent studies on the response of the IVD and stem cells to applied cyclic compression and hydrostatic pressure. These studies investigate the possible role of loading in the initiation and progression of disc degeneration as well as quantifying a physiological loading condition for the study of disc degeneration biological therapy. Subsequently, a possible physiological/beneficial loading range is proposed. This physiological/beneficial loading could provide insight into how to design loading regimes in specific system for the testing of various biological therapies such as cell therapy, chemical therapy or tissue engineering constructs to achieve a better final outcome. In addition, the parameter space of 'physiological' loading may also be an important factor for the differentiation of stem cells towards most ideally 'discogenic' cells for tissue engineering purpose.

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“…Moreover, our study found that the deprivation of glucose in culture medium directly led to the formation of similarly long cell processes when NP cells were in vitro cultured. It has been shown that glucose deprivation leads to the acceleration of disc degeneration and fall in NP cell viability28, 29, and the collapse of nutrition supply pathway of NP is a well-accepted pathogenesis factor of IDD. We proposed that the lack of glucose may be one of the underlying mechanisms of long process formation.…”

Section: Discussionmentioning

confidence: 99%

Insights into the Hallmarks of Human Nucleus Pulposus Cells with Particular Reference to Cell Viability, Phagocytic Potential and Long Process Formation

Chen¹,

Zhang²,

Zhang³

et al. 2013

Int. J. Med. Sci.

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Objective: As a main cellular component within the disc, nucleus pulposus (NP) cells play important roles in disc physiology. However, little is known on the biologic hallmarks of human NP cells. Therefore, the present study aimed to address the features of human NP cells.Methods: Human NP samples were collected from normal cadavers, patients with scoliosis and disc degeneration as normal, disease control and degenerative NP, respectively. The NP samples were studied using transmission electron microscopy and TUNEL assay. Pre-digested NP samples were studied using flow cytometry with PI/Annexin V staining.Results: Both control and degenerative human NP consisted of mainly viable cells with a variety of morphology. Both necrosis and apoptosis were noted in human NP as forms of cell death with increased apoptosis in degenerative NP, which was further confirmed by the TUNEL assay. Phagocytic NP cells had the hallmarks of both stationary macrophages with lysosomes and NP cells with the endoplasmic reticulum. Annulus fibrosus cells have similar morphologic characteristics with NP cells in terms of cell nest, phagocytosis and intracellular organs. Moreover, NP cells with long processes existed in degenerative and scoliotic NP rather than normal NP. When cultured in glucose-free medium, NP cells developed long and thin processes.Conclusion: Human degenerative NP consists of primarily viable cells. We present direct and in vivo evidence that both human annulus fibrosus and NP cells have phagocytic potential. Moreover, NP cells with long processes exist in both scoliotic and degenerative NP with lack of glucose as one of the possible underlying mechanisms.

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Influence of low glucose supply on the regulation of gene expression by nucleus pulposus cells and their responsiveness to mechanical loading

Cited by 32 publications

References 42 publications

Responses of human adipose-derived mesenchymal stem cells to chemical microenvironment of the intervertebral disc

Responses of human adipose-derived mesenchymal stem cells to chemical microenvironment of the intervertebral disc

The effects of dynamic loading on the intervertebral disc

Insights into the Hallmarks of Human Nucleus Pulposus Cells with Particular Reference to Cell Viability, Phagocytic Potential and Long Process Formation

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