Retardation of articular cartilage degradation by glycosaminoglycan polysulfate, pentosan polysulfate, and DH‐40J in the rat air pouch model

Abstract

The rat subcutaneous air pouch model was adapted to examine the in vivo degradation of implanted rabbit articular cartilage, both with and without induced air pouch inflammation, over a 7-day period. The effects of 3 drugs, glycosaminoglycan polysulfate (Arteparon), pentosan polysulfate (SP-54), and zinc-chelated pentosan polysulfate (DH-40J), on inflammationinduced cartilage degradation were also examined. Implanted articular cartilage from noninflamed air pouches showed a reduction in total proteoglycan (PG) content (as hexuronic acid), but not in PG extractability or aggregation, compared with cartilage maintained in tissue culture. The injection of peptone into the air pouch as an inflammogen caused an influx of leukocytes and plasma exudate and a reduction in implanted articular cartilage PG content, extractability, and aggregation, which was significantly greater than that which occurred in noninflamed air pouches. In vitro experiments demonstrated that peptone did not have a direct effect on cartilage PG degradation. Daily injection of Arteparon, SP-54, or DH-40J (10 mg/kg) into pepPresented in part at the 34th Annual Meeting of the Orthopaedic Research Society,

Survey of the therapeutic approach and efficacy of pentosan polysulfate for the prevention and treatment of equine osteoarthritis in veterinary practice inAustralia

“…Respondents also perceived that PPS was more effective as a prophylactic therapy than as treatment for horses with clinical signs of OA. PPS is reported to have various protective and anabolic effects at the cartilage level in various animal models of OA, which includes enhancing proteoglycan synthesis, decreasing the effects of MMPs on cartilage and promoting the production of HA . A recently published study, using an osteochondral fragment model of OA, showed that PPS treatment reduced cartilage fibrillation scores and increased CS 846 epitope concentrations in the synovial fluid of treated horses compared with saline‐treated controls .…”

“…Pentosan polysulfate (PPS) is a semi‐synthetic polysulfated polysaccharide derived from beech wood hemicellulose and reported to modulate the progression of OA . In animal models, PPS has been shown to have an inhibitory effect on matrix metalloproteinases (MMPs), interleukin‐1 and other inflammatory mediators; to increase both the synthesis and molecular weight of hyaluronate (HA); to enhance the uptake of proteoglycan into the extracellular matrix; and to have anti‐inflammatory effects and fibrinolytic activity . However, there is little experimental evidence on the efficacy of PPS for the prevention and treatment of OA in horses .…”

“…7,8 In animal models, PPS has been shown to have an inhibitory effect on matrix metalloproteinases (MMPs), interleukin-1 and other inflammatory mediators; to increase both the synthesis and molecular weight of hyaluronate (HA); to enhance the uptake of proteoglycan into the extracellular matrix; and to have anti-inflammatory effects and fibrinolytic activity. [9][10][11][12][13][14][15][16][17] However, there is little experimental evidence on the efficacy of PPS for the prevention and treatment of OA in horses. 7,8,18 Recently, in an osteochondral fragment model, PPS was shown to reduce cartilage fibrillation scores and to increase chondroitin sulfate (CS 846) epitope concentrations in the synovial fluid of treated horses compared with saline-treated controls.…”

Intradermal air pouch leukocytosis as an in vivo test for nanoparticles

“…7 Thereafter came a period when it was recognized that this model is useful for the study of immune reactions, bone and cartilage breakdown, and also for drug testing. [8][9][10][11][12][13] In addition to cell infiltrations, the production of biological agents, eg, matrix metalloproteinases (MMPs), was studied in the pouch exudates.…”

Effects of intra‐articular sodium pentosan polysulfate and glucosamine on the cytology, total protein concentration and viscosity of synovial fluid in horses

“…[3][4][5][6] In a variety of animal models, PPS has been reported to enhance the synthesis of proteoglycans, maintain the normal articular cartilage ratio of aggrecan to dermatan sulfate, increase the production of hyaluronan (HA), inhibit a number of enzymes responsible for cartilage matrix degeneration, including stromeolysin, and to also have a weak anti-inflammatory effect. [7][8][9] Although the mechanism of action of GLC has not been clearly established, it would appear to have anti-inflammatory effects mediated through a variety of pathways, including inhibition of metalloproteinases, interleukins, tumour necrosis factor, nitric oxide and cyclooxygenase. 3,[10][11][12][13][14] It also appears to enhance protein synthesis, specifically synthesis of aggrecan core protein.…”