Limb mesenchymal cells inhibited from undergoing cartilage differentiation by a tumor promoting phorbol ester maintain expression of the homeobox-containing gene Msx1 and fail to exhibit gap junctional communication.

Tumor promoting phorbol esters are potent inhibitors of the chondrogenic differentiation of limb mesenchymal cells, but the mechanism by which these agents elicit their antichondrogenic effect is unknown. Here we report that limb mesenchymal cells inhibited from undergoing chondrogenesis by a tumor promoting phorbol ester exhibit deregulated expression of the homeobox-containing gene Msx1, a gene implicated in suppressing differentiation of limb mesenchymal cells, and fail to exhibit the extensive gap junctional intercellular communication that normally occurs at the onset of chondrogenesis. These results suggest that tumor promoting activity of phorbol esters may relate to their ability to modulate the expression of regulatory genes involved in controlling terminal differentiation, as well as to their ability to disrupt the intercellular communication involved in initiating the differentiated phenotype of cells.