In vitro hexosamine depletion of intact articular cartilage by e‐prostaglandins

Abstract

Short-term incubations of intact canine articular cartilage slices with prostaglandins E1 and E2 caused significant losses of hexosamine from cartilage matrix compared to controls. Chloroquine, an inhibitor of DNA primer, prevented this prostaglandin-induced hexosamine depletion. These data suggest that E-prostaglandins may degrade articular cartilage directly through DNA-dependent RNA synthesis of cathepsin-like proteases. Catabolism of articular cartilage probably involves degradation of existing matrix in addition to inhibition of synthesis.

Prevention by chloroquine of hexosamine cartilage depletion by e‐prostaglandins

“…But more important is the fact that chloroquine might interfere with PG membrane binding sites which trigger cyclic-AMP production. The results of Teitz and Chrisman (7) cited by Fulkerson et a1 (1) are easily explained by this hypothesis. The intraarticular injection of PG in the rabbit knee induces a synovitis that is not prevented by systemic salicylate, since it is not due to stimulation of PG synthetase but is abolished by systemic chloroquine because of its PG antagonist effect.…”

“…Hong Joon Kim et a1 (1) in reporting 3 cases of reflex sympathetic dystrophy of the knee following meniscectomy pointed out that this had not previously been reported. We have recently seen a further case.…”

“…We read with great interest the paper by Fulkerson et a1 (1) showing that prostaglandins (PG) El and E2 cause a significant loss of hexosamine from cartilage matrix compared to controls, and that this effect is prevented by chloroquine. However, we would like to suggest another interpretation of the effects of this antimalarial drug.…”

Effects of diclofenac, indomethacin, tolfenamic acid and hydrocortisone on prostanoid production in healthy and rheumatic synovial cells

“…In rheumatoid synovitis, the tissue destruction is mostly due to products of biochemically altered synovial cells, such as collagenase, elastase, chymotrypsin-like enzyme and prostanoids (see [24]). The cartilage and bone resorptive activity of PGE 2 has been shown both in vitro and in vivo [6][7][8][9][10]. Various mechanisms involved in this process have been suggested.…”

“…Elevated concentrations of prostaglandins (PG) B, D2, E 2 and F2~ as well as metabolites of prostacyclin and thromboxane A 2 are measurable in synovial fluid from patients with rheumatoid arthritis [3][4][5]. Prostanoids (mainly PGEs) have been shown to augment cartilage and bone destruction in vitro and in vivo [6][7][8][9][10] and in some models to reduce synthesis of connective tissue components [11][12][13]. On the other hand, PGE 2 has been reported to have anti-inflammatory properties in some forms of experimental inflammation (see [1,14]).…”