Inhibition of BMP-induced ectopic bone formation by an antiangiogenic agent (epigallocatechin 3-gallate).

Epigallocatechin 3-gallate (EGCG), which is one of the components of green tea, was recently shown to inhibit endothelial cell growth in vitro and angiogenesis in vivo [5]. We have previously shown that bone and cartilage formation by bone morphogenetic protein (BMP) is highly dependent on the geometry of the carrier (vasculature-inducing or -inhibiting geometry [2]. To verify the function of angiogenesis in the BMP induction system, we examine in this article whether inhibition of angiogenesis enhances chondrogenesis and suppresses osteogenesis. Fibrous glass membrane used as a BMP carrier was mixed with 1.2 micrograms rhBMP-2 and 1-10 micrograms of EGCG and was implanted into rats subcutaneously. As the dose of EGCG increased, alkaline phosphatase activity and calcium content were decreased, whereas the type II collagen content was increased. The results clearly indicated that inhibition of vascularization enhanced chondrogenesis and suppressed osteogenesis.