OPPOSITE EFFECTS OF OSTEOGENIC PROTEIN AND TRANSFORMING GROWTH-FACTOR-BETA ON CHONDROGENESIS IN CULTURED LONG-BONE RUDIMENTS

Osteogenic protein-1 (OF-1, also called BMF-7) is a bone morphogenetic member of the TGF-beta superfamily. In the present study, we examined the effect of recombinant human OP-1 on cartilage and bone formation in organ cultures of metatarsal long bones of mouse embryos and compar ed the OP-1 effects with those of human TGF-beta(1) and porcine TGF-be ta(1) and beta(1). Cartilage formation was determined by measurement o f longitudinal growth of whole bone rudiments during culture and by th e incorporation of (SO4)-S-35 into glycosaminoglycans. Mineralization was monitored by Ca-45 incorporation in the acid-soluble fraction and by measuring the length of the calcifying center of the rudiment. Tolu idine blue-stained histologic sections were used for quantitative hist omorphometric analysis. We found that OP-1 stimulated cartilage growth as determined by sulfate incorporation and that it increased remarkab ly the width of the long bones ends compared with controls. This effec t was partly caused by differentiation of perichondrial cells into cho ndrocytes, resulting in increased appositional growth. In contrast to OP-1, TGF-beta(1) and beta(2) inhibited cartilage growth and reduced t he length of whole bone rudiments compared with controls. In the ossif ying center of the bone rudiments, both OP-1 and TGF-beta inhibited ca rtilage hypertrophy, growth of the bone collar, and matrix mineralizat ion. These data demonstrate that OP-1 and TGF-beta exhibit opposite ef fects on cartilage growth but similar effects on osteogenesis in embry onic mouse long bone cultures. Since both OP-1 and TGF-beta have been demonstrated in embryonic cartilage and bone, these results suggest th at they act as autocrine or paracrine regulators of embryonic bone dev elopment.