Abstract
The overproduction of inorganic pyrophosphate (PPi) by cartilage is thought to be a key element in the formation of calcium pyrophosphate dihydrate (CPPD) crystals in joints, and the subsequent development of pseudogout or chondrocalcinosis. We report herein that transforming growth factor β1 (TGFβ1), alone and in synergy with epidermal growth factor (EGF) or TGFα, markedly stimulates PPi elaboration by porcine articular cartilage in organ culture and monolayer culture. This effect is not seen with platelet‐derived growth factor, basic fibroblast growth factor, or insulin‐like growth factor types 1 and 2, substances which also affect chondrocyte metabolism or are mitogenic. TGFβ1 produces only a modest increase in nucleoside triphosphate pyrophosphohydrolase (NTPPPH), a chondrocyte ectoenzyme that produces PPi; this implies the existence of other pathways for PPi elaboration. TGFβ1 is present in joint fluid and cartilage. TGFβ1, TGFα, and EGF are the first known physiologic modifiers of cartilage PPi production. They provide a novel model for the study of CPPD crystal formation in cartilage, as well as new insights into the pathogenesis of this common affliction of aging.
