Therapeutic treatment of canine osteoarthritis with glycosaminoglycan polysulfuric acid ester

Abstract

The therapeutic effect of glycosaminoglycan polysulfuric acid ester (GAGPS) was studied using the Pond-Nuki model of canine osteoarthritis. The clinical setting was simulated by permitting 4 weeks ambulation without treatment, following anterior cruciate transection. Animals were then injected with GAGPS, 4 mg/kg intramuscularly, twice weekly during weeks 4-8. Control animals received intramuscular saline. The study was terminated 4 weeks after completion of the GAGPS or saline regimen (i.e., 12 weeks postoperatively). Cartilage from the medial femoral condyle was analyzed for collagen integrity (swelling properties), hydroxyproline, uronic acid, active and total proteoglycan (PG)-degrading metalloproteinase, PG-degrading serine proteinase, and histopathology (Mankin score). Condylar cartilage from animals treated with GAGPS demonstrated less cartilage swelling, less total and active metalloproteinase, and lower histopathologic scores Submitted for publication January 9, 1989; accepted in revised form May 30, 1989. than were found in cartilage from saline-treated animals. GAGPS was able to suppress PG-degrading enzyme activity and maintain a more normal-appearing cartilage. It is proposed that GAGPS suppressed PG breakdown by decreasing synthesis of metalloproteinase or by directly inhibiting metalloproteinase in cartilage, rather than by increasing synthesis of PG by chondrocytes.Osteoarthritis (OA) is a common disorder that affects over 40 million Americans (1). OA cartilage is characterized by loss of proteoglycan (PG), disruption of the collagen network, and eventual exposure of the underlying subchondral bone. Current therapy for patients with OA is primarily palliative and comprises a combination of physical, psychologic, surgical, and medicinal approaches, including the use of antiinflammatory agents. These measures have not been demonstrated to alter the progression of OA.There is a new avenue of research focusing on agents that can slow or reverse the progression of OA lesions. One prototypic agent that may alter cartilage degradation is glycosaminoglycan polysulfuric acid ester (GAGPS), an extract of bovine lung and tracheal tissue that has been sulfate-esterified and then purified. GAGPS has been found to stimulate GAG synthesis in vitro (2), inhibit collagen and PG catabolism (3), and inhibit several enzymes, such as hyaluronidase, cathepsin B 1, elastase, collagenase, and a neutral metalloproteinase that degrades PGs (3,4).Matrix proteoglycans play an important role in the structural integrity of cartilage. Mankin et a1 (5) and Ehrlich (6) found a loss of matrix PGs in cultured OA cartilage, which suggests degradative activity. Enzymes that can degrade PG at physiologic pH have

Systematic review of the management of canine osteoarthritis

“…Pharmacological agents There were 40 studies of pharmacological agents as symptom-modifying agents, structure-modifying agents, or both (Altman and others 1989a, b, Howell and others 1991, Myers and others 1991, 1999, Rogachefsky and others 1993, Fernandes and others 1995, 1998, Vasseur and others 1995, Carney 1996, Read and others 1996, Yu and others 1996, Jovanovic and others 1997, Budsberg and others 1999, 2007, Manicourt and others 1999, Pelletier and others 1999, 2005, Smith and others 1999, Doig and others 2000, Innes and others 2000, Boileau and others 2002, Lipscomb and others 2002, Nell and others 2002, Hazewinkel and others 2003, Moreau and others 2003, 2006, 2007, Behets and others 2004, El Hajjaji and others 2004, Lajeunesse and others 2004, Pardy and others 2004, Peterson and Keefe 2004, Hanson and others 2006, Karsdal and others 2006, Mastbergen and others 2006, Pollmeier and others 2006, Ryan and others 2006, Brainard and others 2007, Mansa and others 2007). …”

Effects of chondroitin sulfate and sodium hyaluronate on chondrocytes and extracellular matrix of articular cartilage in dogs with degenerative joint disease

“…It cannot be affirmed which sodium hyaluronate medicated by intravenous injection reached the minimum effective concentration at the cartilaginous joint tissue, providing adequate action of this drug because the hyaluronic acid molecule has a plasmatic half-life of several minutes (Prestwich and Vercruysse, 1998). Moreover, sodium hyaluronate has a viscosupplementation effect when used by intraarticular via, which improves the viscosity of the synovial fluid, decreasing attrition and impact on the injured cartilage, however, this is a short duration effect (Balazs and Denlinger, 1993). Smith et al (1998) did not observe improvement in the cartilage morphology using this drug by intraarticular access either.…”

Effect of Polysulfated Glycosaminoglycan on DNA Content and Proteoglycan Metabolism in Normal and Osteoarthritic Canine Articular Cartilage Explants

“…Both monoiodoacetate and corticosteroids (at high doses) cause chondrolysis. PSGAG ameliorated articular cartilage degeneration in immobilization and partial meniscectomy models of OA as judged by histologic‐based cell counts 11,36–38 …”