High susceptibility of human articular cartilage glycosaminoglycan synthesis to changes in inorganic sulfate availability

Abstract

The effect of sulfate concentration in the medium on glycosaminoglycan synthesis in articular cartilage of five different species was examined in relation to the physiological serum sulfate concentration in these species. Only the rate of sulfated glycosaminoglycan synthesis in human articular cartilage was sensitive to small deviations from the physiological sulfate concentration. A reduction in the sulfate concentration from 0.3 mM (physiological) to 0.2 mM resulted in a 33% reduction in glycosaminoglycan synthesis. In addition, we studied the effect of arthritic and "osteoarthritic" alterations in murine cartilage on the dependence of glycosaminoglycan synthesis on low sulfate concentrations. Arthritic and "osteoarthritic" cartilage had a similar dependence on the sulfate concentration in the medium as normal cartilage. Glycosaminoglycan synthesis in human articular cartilage appears to be very sensitive to the potential sulfate-depleting effects of drugs used in the treatment of rheumatoid arthritis and osteoarthritis.

Sulphate and osteoarthritis: decrease of serum sulphate levels by an additional 3-h fast and a 3-h glucose tolerance test after an overnight fast

“…Using cultures of human 1 and other animal 2 cell types, we and others 3 have found that sulphation of chondroitin in cultured cells is usually lowered when sulphate concentrations in culture medium are ,0.2 mmol/l. Normal fasting sulphate concentrations in adult humans are lower than those in any animals that have been tested, 4 generally averaging between 0.25 and 0.4 mmol/l, [4][5][6] with a few people reported to have concentrations as low as 0.1 mmol/l.…”

Critical role of vitamin D in sulfate homeostasis: regulation of the sodium-sulfate cotransporter by 1,25-dihydroxyvitamin D3

“…The former may represent a direct effect of a decreased inorganic sulfate pool, inasmuch as decreased availability of sulfate may affect intracellular sulfation of cellular components such as proteoglycans. It has been reported that proteoglycan sulfation in articular cartilage is dependent on the inorganic sulfate concentration in the media (42). The latter finding suggests that chronic sulfate wasting may ultimately cause a reduction in the organic sulfate pool, because methionine and cysteine can be metabolized to glutathione, taurine, or inorganic sulfate (21).…”

Anti-inflammatory action of sulfated glucosamine on cytokine regulation in LPS-activated PMA-differentiated THP-1 macrophages

“…Except for hyaluronate, all glycosaminoglycans contain sulfate groups in ester bonds with the OH groups of their amino sugar residues. Additionally, previous studies have not only demonstrated that sulfate deficiency reduced normal synthesis of glycosaminoglycan, but also that sulfur has beneficial effects on patients with chronic inflammation such as arthritis [25,26]. The negatively-charged sulfate groups may act as radical scavengers that affect anti-inflammatory processes as inhibitors of iNOS and COX activity [27].…”