The Effect of Lactate and pH on Proteoglycan and Protein Synthesis Rates in the Intervertebral Disc

Ohshima, Hiroshi; Urban, J

doi:10.1097/00007632-199209000-00012

Cited by 211 publications

(155 citation statements)

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“…For both disc and cartilage cells cultured for 48 h in alginate beads, the production of matrix components showed a biphasic response to pH (Fig. 1), as seen previously after short exposures of disc explants and cartilage cells in suspension culture to changes in extracellular pH [39,54]. Rates were highest at around pH 7.0-7.2 (the estimated pH in normal discs [19]), where they were 10-20% greater than at pH 7.4 (the extracellular pH of most body fluids).…”

Section: Discussionsupporting

confidence: 79%

“…1a). Protein synthesis appeared less sensitive to pH, as observed in similar systems [39,54], but was still strongly inhibited under acid conditions (Fig. 1b).…”

Section: Discussionsupporting

confidence: 70%

“…sis and production of proteases. Matrix acidity is another important factor governing matrix production; a fall in matrix pH has been shown to modify protein and proteoglycan synthesis by intervertebral disc explants [39] as in other cartilages [12]. How such factors alter the production and activity of degradative enzymes is, however, relatively unexplored.…”

Section: Introductionmentioning

confidence: 99%

“…We compared the behaviour of nucleus pulposus cells to that of articular chondrocytes as, although in many respects the cellular environment of these two cell types is similar, the disc cells are routinely exposed to more acidic values of extracellular pH in vivo [13,24]. We used isolated cells rather than the explants used in previous studies [12,39], because in explant cultures, extracellular pH is modified by matrix properties, varies throughout the explant and is difficult to control [5]. The effects of pH were assessed on some species involved in matrix turnover; proteoglycan and protein synthesis were determined using radiotracer incorporation, enzymes involved in matrix degradation, (MMPs) and their inhibitors (TIMPs) were assessed using fluorescent substrate cleavage, MMP-2 and -9 were measured by gelatin zymography, TIMP-1 and -2 activities were detected using an immunoassay kit and ELISA system respectively.…”

Section: Introductionmentioning

confidence: 99%

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The effect of extracellular pH on matrix turnover by cells of the bovine nucleus pulposus

Razaq

Wilkins

Urban

2003

European Spine Journal

172

164

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IntroductionNucleus pulposus cells are solely responsible for the production and maintenance of the extracellular matrix of the nucleus throughout life [31]. The cells have no direct contact with each other and rely on cell-matrix interactions and signals from the environment to maintain the function of the tissue. The cells synthesize all the matrix components [10,37,38,50] and also produce degradative enzymes including metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of metalloproteinases or TIMPs), involved in matrix turnover [7,45,53]. The fine balance between synthesis of components and the breakdown of tissue determines the composition of the matrix; tissue integrity is thus dependent on the activity of the nucleus pulposus cells [53]. In vivo [20,43] and in vitro [14] environmental factors such as mechanical stress [30,34] and nutrient levels have been found to affect matrix composition, presumably by affecting macromolecule biosyntheAbstract It has long been known that very acidic conditions can be found in degenerate discs. The effect of these acid conditions on matrix turnover are, however, unknown. This study aimed to examine the effect of acidity on production of matrix components and on agents which break down the matrix in order to gain insight into the effect of pathological values of pH on matrix turnover. Cells were isolated from the nucleus of bovine discs and from bovine articular cartilage, embedded in alginate beads and cultured at pH levels maintained within the ranges seen in normal and pathological discs: pH 7.4-pH 6.3 for 48 h. Rates of sulphated glycosaminoglycan (GAG) and protein synthesis were measured, as well as rates of production of some agents involved in matrix breakdown, i.e. total and activated matrix metalloproteinases (MMPs) and their inhibitors (TIMPs). The results showed that acid conditions had a profound effect on cell matrix turnover; at pH 6.4, total production of most species measured was inhibited by more than 50% compared to production at pH 7.2; production of sulphated GAGs and of TIMP-1 fell by >90%. However production of active metalloproteinases by disc cells was relatively insensitive to pH, with activity at pH 6.3 not statistically different from that at pH 7.2. These findings indicate that exposure to acid conditions appears particularly deleterious for the disc matrix, as it inhibits the disc cells from synthesising functionally important molecules such as the sulphated GAGs but does not prevent the production of agents able to degrade matrix components. The low values of pH seen in some degenerate discs are thus likely to be involved in breakdown of the disc matrix.

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Section: Discussionsupporting

confidence: 79%

“…1a). Protein synthesis appeared less sensitive to pH, as observed in similar systems [39,54], but was still strongly inhibited under acid conditions (Fig. 1b).…”

Section: Discussionsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The effect of extracellular pH on matrix turnover by cells of the bovine nucleus pulposus

Razaq

Wilkins

Urban

2003

European Spine Journal

172

164

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“…17 Accumulation of lactic acid decreases disc pH (to near pH 6.3) and is detrimental to the matrix as it decreases glycosaminoglycan production, tissue inhibitor of metalloproteinase (TIMP) production, and cell viability. 16,[18][19][20] Further, serum deprivation results in decreased cell proliferation and increased cell senescence. 21 The direct effect of hypoxia is mixed.…”

Section: Pathophysiology Of Clbpmentioning

confidence: 99%

New Challenges for Intervertebral Disc Treatment Using Regenerative Medicine

Masuda

Lotz

2010

Tissue Engineering Part B: Reviews

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Rheological characterization of photopolymerized poly(vinyl alcohol) hydrogels for potential use in nucleus pulposus replacement

Bader

Rochefort

2007

J Biomedical Materials Res

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Hydrogels have been proposed as candidates for nucleus pulposus replacement because of their similarity in mechanical behavior to the native tissue when subjected to transient or static loading; however, given the viscoelastic nature of soft biological tissues, the lack of dynamic testing is a significant inadequacy in the studies performed to date. In the present work, the viscoelastic behavior of a hydrogel system obtained via photopolymerization of glycidyl methacrylate modified poly(vinyl alcohol) (PVA) was evaluated in comparison to that of the nucleus pulposus when subjected to dynamic torsional shear. The complex shear moduli and phase shift angles were modulated through the variation of PVA molecular weight and concentration of polymer prior to photopolymerization. Hydrolysis resistance was assessed by evaluation of the viscoelastic behavior of hydrogels submerged in Hank's solution for progressively longer periods of time. The phase shift angles of all hydrogels were lower than those of the nucleus pulposi; however, the complex shear moduli of the synthetic system spanned the values observed for the natural system. Over the time frame of the experiment, no changes in moduli were observed following submersion in Hank's solution. This study represents the first attempt to successfully mimic the viscoelastic nature of the nucleus pulposus exhibited under dynamic torsional loading with that of materials intended for use in tissue replacement.

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The Effect of Lactate and pH on Proteoglycan and Protein Synthesis Rates in the Intervertebral Disc

Cited by 211 publications

References 0 publications

The effect of extracellular pH on matrix turnover by cells of the bovine nucleus pulposus

The effect of extracellular pH on matrix turnover by cells of the bovine nucleus pulposus

New Challenges for Intervertebral Disc Treatment Using Regenerative Medicine

Rheological characterization of photopolymerized poly(vinyl alcohol) hydrogels for potential use in nucleus pulposus replacement

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