Effect of FK506 on osteoinduction by recombinant human bone morphogenetic protein-2.
FK506 is an immunosuppressant that is used widely in organ transplantation, and it has recently been recognized as effective for promoting the growth of bone grafts [J. Bone Miner. Res. 15 (2000) 1147]. In this study, we evaluated the influence of FK506 on osteoinduction by recombinant human bone morphogenetic protein-2 (rhBMP-2) using atelopeptide type I collagen as a carrier. We administered FK506 (1 mg/kg/day intramuscularly) on days -2 to 0, -2 to 7, and -2 to sacrifice. rhBMP-2 was implanted into the calf muscle of Wistar rats (thirty per group) and the implant was sampled on days 7, 14, and 21. Radiographic evaluation, histological examination, and biochemical analysis were performed. It was found that FK506 promoted the early stage of osteoinduction after short-term administration. However, long-term administration of this agent accelerated both bone formation and bone resorption. In order to use FK506 effectively for promoting bone growth, we must further examine the appropriate dose, method, and period of administration.
Kaihara
Shinji
S
Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Japan.
Bessho
Kazuhisa
K
Okubo
Yasunori
Y
Sonobe
Junya
J
Kusumoto
Kenji
K
Ogawa
Yutaka
Y
Iizuka
Tadahiko
T
D000469:Alkaline Phosphatase / Q000032:analysis; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000494:pharmacology*; D001842:Bone and Bones / Q000033:anatomy & histology / Q000737:chemistry; D002118:Calcium / Q000032:analysis; D002356:Cartilage / Q000033:anatomy & histology; D003094:Collagen / Q000008:administration & dosage; D004337:Drug Carriers; D004347:Drug Interactions; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009132:Muscles / Q000000981:diagnostic imaging; D010012:Osteogenesis; D011859:Radiography; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D016559:Tacrolimus / Q000494:pharmacology*; D016212:Transforming Growth Factor beta
C525718:BMP2 protein, human; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D004337:Drug Carriers; D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C059821:atelocollagen; C499469:recombinant human bone morphogenetic protein-2; D003094:Collagen; D000469:Alkaline Phosphatase; D002118:Calcium; D016559:Tacrolimus