title: The effect of extracellular pH on matrix turnover by cells of the bovine nucleus pulposus.
abstract: 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.
authors.affiliation: University Laboratory of Physiology, University of Oxford, Parks Road, OX1 3PT, Oxford, UK.
authors.forename: Sajjad
authors.initials: S
authors.lastname: Razaq
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wilkins
authors.forename: Jill P G
authors.initials: JP
authors.lastname: Urban
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007403:Intervertebral Disc / Q000166:cytology / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism
chemical_list: D006025:Glycosaminoglycans; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases