TRANSFORMING GROWTH FACTOR-BETA-1 STIMULATES INORGANIC PYROPHOSPHATE ELABORATION BY PORCINE CARTILAGE

The overproduction of inorganic pyrophosphate (PP(i)) 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 beta-1 (TGF-beta-1), alone and in synergy with epidermal growth factor (EGF) or TGF-alpha, markedly stimulates PP(i) 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. TGF-beta-1 produces only a modest increase in nucleoside triphosphate pyrophosphohydrolase (NTPPPH), a chondrocyte ectoenzyme that produces PP(i); this implies the existence of other pathways for PP(i) elaboration. TGF-beta-1 is present in joint fluid and cartilage. TGF-beta-1, TGF-alpha, and EGF are the first known physiologic modifiers of cartilage PP(i) 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.