Effect of Porcine Fetal Enamel Matrix Derivative on Chondrocyte Proliferation, Differentiation, and Local Factor Production Is Dependent on Cell Maturation State

Abstract

Recent studies have shown that porcine fetal enamel matrix derivative (EMD) can enhance the osteoinductive ability of demineralized freeze-dried bone allograft (DFDBA) in a nude mouse muscle implantation model. This suggests that one or more components of EMD can regulate the process of endochondral ossification initiated by DFDBA. To substantiate this hypothesis, in the current study, chondrocytes in the endochondral pathway at two stages of maturation were tested for their response to EMD. Chondrocytes were isolated from the resting zone and growth zone (prehypertrophic and upper hypertrophic cell zones) of the costochondral growth plate cartilage of adolescent rats. The results showed that the relatively immature resting zone cells responded to EMD with an increase in proliferation and a decrease in differentiation as measured by alkaline-phosphatase-specific activity. In addition, EMD stimulated a fivefold increase in PGE₂ production, but was without effect on collagen synthesis, proteoglycan sulfation, and TGF-β₁ production. The more mature growth zone cells also responded to EMD with increased proliferation, but alkaline-phosphatase-specific activity was unchanged, and there was only a modest increase in PGE₂ production. In contrast to resting zone cells, growth zone cells exhibited a decrease in collagen synthesis, proteoglycan sulfation, and TGF-β₁ production. These observations indicate that EMD has prominent effects on cells in the endochondral pathway. In particular, EMD stimulates the production of more cells, but inhibits their maturation. This would increase the pool of cells available for subsequent differentiation in response to other factors.