TRANSFORMING GROWTH-FACTOR-BETA MODULATION OF GLYCOSAMINOGLYCAN PRODUCTION BY MESENCHYMAL CELLS OF THE DEVELOPING MURINE SECONDARY PALATE

Development of the mammalian secondary palate requires proper production of the extracellular matrix, particularly glycosaminoglycans (GAGs) and collagen. Endogenous factors that regulate the metabolism of these molecules are largely undefined. A candidate for a locally derived molecule would be transforming growth factor β1(TGFβ1) by virtue of its potency as a modulator of extracellular matrix metabolism by several cell lines. We have thus attempted to assign a regulatory role for TGFβ1 in modulation of GAG production and degradation by mesenchymal cells of the murine embryonic palate (MEPM). Treatment with TGFβ1 or TGFβ2, but not IGF-II, resulted in a stimulation of total GAG synthesis. Furthermore, cells treated with bothTGFβ1 and TGFα showed a synergistic increase in GAG synthesis if pretreated with TGFβ1 but not TGFα. Simultaneous stimulation with TGFβ1 and TGFβ2 did not elicit a synergistic response. These studies demonstrate the ability of TGFβ, synthesized by embryonic palatal cells, to specifically stimulate GAG synthesis by MEPM cells. Other growth factors present in the developing craniofacial region may also modulate TGFβ-induced GAG synthesis, a biosynthetic process critical to normal development of the embryonic palate. © 1991.