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.
Takita
Hiroko
H
Department of Oral Health Science, Graduate School of Dental Medicine, Hokkaido University, N-13, W-7, Kita-ku, Sapporo 060-8586, Japan. htakita@den.hokudai.ac.jp
Kikuchi
Masahiro
M
Sato
Yasuko
Y
Kuboki
Yoshinori
Y
D000469:Alkaline Phosphatase / Q000378:metabolism; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage; D001842:Bone and Bones; D002118:Calcium / Q000378:metabolism; D002356:Cartilage / Q000187:drug effects / Q000254:growth & development; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002828:Choristoma / Q000139:chemically induced* / Q000517:prevention & control*; D024043:Collagen Type II / Q000378:metabolism; D016503:Drug Delivery Systems; D006801:Humans; D008297:Male; D010012:Osteogenesis / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012871:Skin Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D016212:Transforming Growth Factor beta
D020533:Angiogenesis Inhibitors; C525718:BMP2 protein, human; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D024043:Collagen Type II; D016212:Transforming Growth Factor beta; D002392:Catechin; C045651:epigallocatechin gallate; D000469:Alkaline Phosphatase; D002118:Calcium