Effects of phorbol-12-myristate-13-acetate on the phenotypic program of cultured chondroblasts and fibroblasts.

Phorbol-12-myristate-13-acetate (PMA) has a prompt, differential, and partially reversible effect on cultured chick chondroblasts. Within 36 hr PMA transforms sessile, polygonal, epithelioid chondroblasts into motile, multilayered, fibroblastic cells. In PMA chick chondroblasts rapidly cease to synthesize two of their terminal luxury molecules, the type IV sulfated proteoglycan that characterizes the extracell matrix and a glycosylated protein with an apparent molecular weight of 180,000. This glycosylated protein constitutes approximately 5% of the total protein in normal chondroblasts. If returned to normal medium after 4 days in PMA, virtually 100% of the cells reinitiate the synthesis of their type IV sulfated proteoglycan, of the 180,000-dalton protein, and reacquire their polygonal, epithelioid morphology. If returned to normal medium after 12 days in PMA, the cells fail to synthesize their two characteristic luxury molecules, and 100% of the cells remain fibroblastic. PMA alters the morphology of chick fibroblasts but does not block synthesis of their characteristic type III sulfated proteoglycan. PMA proves to be a mitogen for chondroblasts but not for fibroblasts, in spite of the phenotypic similarities of these two cell types.