Avocado/Soybean Unsaponifiables, Glucosamine and Chondroitin Sulfate Combination Inhibits Proinflammatory COX-2 Expression and Prostaglandin E2 Production in Tendon-Derived Cells

Tendinopathy, a common disorder in man and horses, is characterized by pain, dysfunction, and tendon degeneration. Inflammation plays a key role in the pathogenesis of tendinopathy. Tendon cells produce proinflammatory molecules that induce pain and tissue deterioration. Currently used nonsteroidal anti-inflammatory drugs are palliative but have been associated with adverse side effects prompting the search for safe, alternative compounds. This study determined whether tendon-derived cells' expression of proinflammatory cyclooxygenase (COX)-2 and production of prostaglandin E2 (PGE(2)) could be attenuated by the combination of avocado/soybean unsaponifiables (ASU), glucosamine (GLU), and chondroitin sulfate (CS). ASU, GLU, and CS have been used in the management of osteoarthritis-associated joint inflammation. Tenocytes in monolayer and microcarrier spinner cultures were incubated with media alone, or with the combination of ASU (8.3 mu g/mL), GLU (11 mu g/mL), and CS (20 mu g/mL). Cultures were next incubated with media alone, or stimulated with interleukin-1 beta (IL-1 beta; 10 ng/mL) for 1 h to measure COX-2 gene expression, or for 24 h to measure PGE(2) production, respectively. Tenocyte phenotype was analyzed by phase-contrast microscopy, immunocytochemistry, and Western blotting. Tendon-derived cells proliferated and produced extracellular matrix component type I collagen in monolayer and microcarrier spinner cultures. IL-1 beta-induced COX-2 gene expression and PGE(2) production were significantly reduced by the combination of (ASU+GLU+CS). The suppression of IL-1 beta-induced inflammatory response suggests that (ASU+GLU+CS) may help attenuate deleterious inflammation in tendons.