Chondrogenesis in chick limb bud mesodermal cells: reciprocal modulation by activin and inhibin

Activin and inhibin are members of the transforming growth factor-beta superfamily sharing a common beta-subunit, but with opposite biological activities on the release of follicle-stimulating hormone from pituitary. Recent studies have demonstrated that activin is the long sought after mesoderm induction factor in amphibians. To determine if activin and inhibin affect the proliferation and differentiation of chick limb bud mesodermal cells during cartilage formation of the limb, recombinant human activin A and inhibin A were tested on stage 24 chick limb bud mesodermal cells. The results showed that activin A has an inhibitory effect on chondrogenic differentiation, as indicated by Alcian blue staining and decreased [35S]sulfate incorporation into proteoglycans. In addition, the expression of type II collagen mRNA, a specific phenotypic marker of cartilage, was greatly inhibited when cultures were exposed to activin A for 5 days at a dose of 10 ng/ml. In contrast, inhibin A stimulated cartilage formation, as indicated by increased expression of type II collagen mRNA and synthesis of proteoglycans. These results imply that activin A and inhibin A can modulate chondrogenesis during differentiation of limb bud cells in culture.