Histological investigation of osteoinductive properties of rh-BMP2 in a rat calvarial bone defect model.
BACKGROUND
Recombinant human bone morphogenetic protein-2 (rh-BMP2) has osteoinductive properties. The sequence of osteogenesis induced by rh-BMP2 in a rat calvarial bone defect model was evaluated histologically.


METHODS
Atelopeptide type I collagen was selected as the carrier matrix for rh-BMP2. This collagen was mixed with 50 microg of rh-BMP2 and treated by lyophilization to make a suitable form for filling bone defects. Thirty Wistar rats (male; 10 weeks old) underwent craniotomy resulting in a round bone defect with a diameter of 4 mm. Three weeks after the operation, the defect site was exposed to implant collagen with rh-BMP2 in the experimental group and collagen only in the control group. Three, 6 and 9 weeks after implantation, calvarial specimens were harvested and stained with haematoxylin/eosin. In addition, bromodeoxyuridine (BrdU) immunohistochemical staining was performed.


RESULTS
In the experimental group, marked ossification was found. In contrast, there was no tendency towards osteogenesis in the control group, 9 weeks after collagen implantation. In BrdU immunohistochemical staining, the number of BrdU-positive cells was significantly higher in the experimental group than in the control group, and was significantly higher at the periosteal site than at other sites at 3 and 6 weeks after implantation.


CONCLUSIONS
rh-BMP2 exhibited osteoinductive properties, and markedly stimulated proliferation of periosteal cells.
Inoda
Hirosato
H
Department of Oral and Maxillofacial Surgery, Shiga University of Medical Science, Otsu, Japan. inoda@belle.shiga-med.ac.jp
Yamamoto
Gaku
G
Hattori
Takanori
T
D000818:Animals; D000963:Antimetabolites; D001847:Bone Diseases / Q000188:drug therapy*; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000627:therapeutic use*; D001973:Bromodeoxyuridine; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen; D004396:Coloring Agents; D004195:Disease Models, Animal; D004337:Drug Carriers; D004801:Eosine Yellowish-(YS); D005456:Fluorescent Dyes; D006416:Hematoxylin; D006801:Humans; D008297:Male; D010012:Osteogenesis / Q000187:drug effects*; D010521:Periosteum / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D012886:Skull / Q000187:drug effects* / Q000473:pathology; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000627:therapeutic use*
D000963:Antimetabolites; C525718:BMP2 protein, human; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D004396:Coloring Agents; D004337:Drug Carriers; D005456:Fluorescent Dyes; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C059821:atelocollagen; C499469:recombinant human bone morphogenetic protein-2; D003094:Collagen; D001973:Bromodeoxyuridine; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin