Enhanced effects of BMP-binding peptide combined with recombinant human BMP-2 on the healing of a rodent segmental femoral defect.
BMP-binding peptide (BBP) enhances the osteogenic activity of recombinant human bone morphogenetic protein-2 (rhBMP-2), but the mechanism underlying the enhancement remains unclear. We aimed to elucidate the potential enhanced efficacy of BBP using critical-sized segmental femoral bone defects in rats. Seventy defects in seven groups of rats were filled with various amounts (0, 2, 5, and 10 microg) of rhBMP-2 with or without 1000 microg BBP. Radiographs were obtained after 4 and 8 weeks. The animals were euthanized at 8 weeks, and femoral specimens were assessed manually, evaluated for bone volume using microcomputed tomography, and subjected to histological or biomechanical analysis. Although 10 microg rhBMP-2 yielded consistent results in terms of bone healing and quality of bone repair across the segmental defect, lower doses of rhBMP-2 failed to induce satisfactory bone healing. However, the combined administration of lower doses of rhBMP-2 and BBP induced the formation of significantly large amounts of bone. Our results suggest that the combined administration of rhBMP-2 and BBP facilitates bone healing and has potential clinical applications.
Morishita
Yuichiro
Y
Department of Orthopaedic Surgery, Fukuoka University, Fukuoka, Japan.
Naito
Masatoshi
M
Miyazaki
Masashi
M
He
Wubing
W
Wu
Guizhong
G
Wei
Feng
F
Sintuu
Chananit
C
Hymanson
Henry
H
Brochmann
Elsa J
EJ
Murray
Samuel S
SS
Wang
Jeffrey C
JC
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage*; D001861:Bone Regeneration / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination / Q000379:methods; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects / Q000293:injuries*; D017102:Fracture Healing / Q000187:drug effects; D050723:Fractures, Bone / Q000000981:diagnostic imaging / Q000188:drug therapy*; D008297:Male; D023421:Models, Animal; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000008:administration & dosage*; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*; D016896:Treatment Outcome; D055114:X-Ray Microtomography
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2