Osteoinduction capability of recombinant human bone morphogenetic protein-2 in intramuscular and subcutaneous sites: an experimental study.
The osteoinduction capability of recombinant human bone morphogenetic protein-2 (rhBMP-2) in the muscle and in the subcutaneous tissue in Wistar rats (n = 20) was evaluated, using atelopeptide type-I collagen as a carrier. The alkaline phosphatase (ALP) activity and calcium (Ca) content were quantitatively analyzed 1, 3, 7 and 21 days after the implantation of 5 micrograms of rhBMP-2. At 3 days, the ALP activity began to increase gradually. The Ca content showed a slow increase until 7 days and was markedly elevated at 21 days. There was no significant difference observed between the intramuscular and subcutaneous sites until 3 days. However, at 7 days, both the ALP activity and Ca content were significantly higher intramuscularly than subcutaneously. Also, at 21 days they were higher in the muscle than in the subcutaneous tissue. These results suggest that the difference in osteoinduction could be related to the partial pressure of oxygen or the blood supply in the intramuscular and subcutaneous sites, and that immature mesenchymal cells in the muscle could more easily differentiate into osteoblasts, leading to osteoinduction. This study clearly demonstrated that even a small amount (5 micrograms) or rhBMP-2 induces new bone in the subcutaneous tissue, which has a lesser blood flow than the muscle.
Yoshida
K
K
Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Kyoto University, Japan.
Bessho
K
K
Fujimura
K
K
Kusumoto
K
K
Ogawa
Y
Y
Tani
Y
Y
Iizuka
T
T
D000469:Alkaline Phosphatase / Q000032:analysis; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D001842:Bone and Bones / Q000737:chemistry / Q000201:enzymology; D002118:Calcium / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D003094:Collagen; D004337:Drug Carriers; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects; D018482:Muscle, Skeletal / Q000098:blood supply / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology; D009999:Ossification, Heterotopic / Q000139:chemically induced* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D010006:Osteoblasts / Q000166:cytology; D010012:Osteogenesis; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D012867:Skin / Q000098:blood supply / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000494:pharmacology*
C525718:BMP2 protein, human; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D004337:Drug Carriers; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C059821:atelocollagen; C499469:recombinant human bone morphogenetic protein-2; D003094:Collagen; D000469:Alkaline Phosphatase; D010100:Oxygen; D002118:Calcium