Effect of recombinant human bone morphogenetic protein-2, -4, and -7 on bone formation in rat calvarial defects

Suk Ju Hyun, Dong Kwan Han, Seongho Choi, Jung Kiu Chai, Kyoo Sung Cho, Chong Kwan Kim, ChangSung Kim

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Background: Currently, more than 20 bone morphogenetic proteins (BMPs) have been identified, and many trials have been carried out using recombinant human BMPs (rhBMPs) for bone tissue engineering. However, comparative analyses on bone formative activities of rhBMP using a preclinical model have been limited. Therefore, the aim of this study was to evaluate and compare the osteogenic potential of rhBMP-2, -4, and -7 delivered with absorbable collagen sponge (ACS) upon early (2 weeks) and complete (8 weeks) wound healing phases in a critical sized rat calvarial defect model. Methods: Eight-millimeter critical sized calvarial defects were created in 30 male Sprague-Dawley rats. The animals were divided into three groups of 10 animals each. The defects were treated with 0.025 mg/ml rhBMP-2/ACS, rhBMP-4/ACS, or rhBMP-7/ACS. The rats were sacrificed at either 2 (five rats) or 8 (five rats) weeks after surgery, and the results were evaluated histologically, histomorphometrically, and immunohistometrically. Results: The surgical implantation of rhBMP-2/ACS, rhBMP-4/ACS, or rhBMP-7/ACS resulted in enhanced local bone formation in the rat calvarial defect model at both 2 and 8 weeks. The amount of defect closure, new bone area, and bone density were similar in the three groups at each time point (P>0.05). In terms of bone density and new bone area, there were statistically significant differences between results obtained at 2 weeks and those obtained at 8 weeks in all groups (P<0.05). Two-way analysis of variance (ANOVA) revealed that there was no correlation between the time and conditions (P>0.05), but time was found to have a strong influence on defect closure, new bone area, and bone density (P<0.05). Irrespective of rhBMP type, positive immunoreactions of osteopontin (OPN) and osteocalcin (OCN) were evident at 2 and 8 weeks. Intense OPN and OCN staining was observed near the newly formed bone as well as in some cells within the new bone. Conclusions: Within the rhBMP types used, rhBMP concentration, and the observation interval, there appears to be no specific differences in bone regenerative potential. All rhBMPs used in this study may be considered effective factors for inducing bone formation.

Original languageEnglish
Pages (from-to)1667-1674
Number of pages8
JournalJournal of Periodontology
Volume76
Issue number10
DOIs
Publication statusPublished - 2005 Oct 1

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Osteogenesis
Porifera
Collagen
Bone and Bones
Bone Density
Bone Morphogenetic Proteins
Osteopontin
Osteocalcin
recombinant human bone morphogenetic protein-2
human BMP4 protein
Tissue Engineering
Wound Healing
Sprague Dawley Rats
Observation
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Dentistry(all)

Cite this

Hyun, Suk Ju ; Han, Dong Kwan ; Choi, Seongho ; Chai, Jung Kiu ; Cho, Kyoo Sung ; Kim, Chong Kwan ; Kim, ChangSung. / Effect of recombinant human bone morphogenetic protein-2, -4, and -7 on bone formation in rat calvarial defects. In: Journal of Periodontology. 2005 ; Vol. 76, No. 10. pp. 1667-1674.
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title = "Effect of recombinant human bone morphogenetic protein-2, -4, and -7 on bone formation in rat calvarial defects",
abstract = "Background: Currently, more than 20 bone morphogenetic proteins (BMPs) have been identified, and many trials have been carried out using recombinant human BMPs (rhBMPs) for bone tissue engineering. However, comparative analyses on bone formative activities of rhBMP using a preclinical model have been limited. Therefore, the aim of this study was to evaluate and compare the osteogenic potential of rhBMP-2, -4, and -7 delivered with absorbable collagen sponge (ACS) upon early (2 weeks) and complete (8 weeks) wound healing phases in a critical sized rat calvarial defect model. Methods: Eight-millimeter critical sized calvarial defects were created in 30 male Sprague-Dawley rats. The animals were divided into three groups of 10 animals each. The defects were treated with 0.025 mg/ml rhBMP-2/ACS, rhBMP-4/ACS, or rhBMP-7/ACS. The rats were sacrificed at either 2 (five rats) or 8 (five rats) weeks after surgery, and the results were evaluated histologically, histomorphometrically, and immunohistometrically. Results: The surgical implantation of rhBMP-2/ACS, rhBMP-4/ACS, or rhBMP-7/ACS resulted in enhanced local bone formation in the rat calvarial defect model at both 2 and 8 weeks. The amount of defect closure, new bone area, and bone density were similar in the three groups at each time point (P>0.05). In terms of bone density and new bone area, there were statistically significant differences between results obtained at 2 weeks and those obtained at 8 weeks in all groups (P<0.05). Two-way analysis of variance (ANOVA) revealed that there was no correlation between the time and conditions (P>0.05), but time was found to have a strong influence on defect closure, new bone area, and bone density (P<0.05). Irrespective of rhBMP type, positive immunoreactions of osteopontin (OPN) and osteocalcin (OCN) were evident at 2 and 8 weeks. Intense OPN and OCN staining was observed near the newly formed bone as well as in some cells within the new bone. Conclusions: Within the rhBMP types used, rhBMP concentration, and the observation interval, there appears to be no specific differences in bone regenerative potential. All rhBMPs used in this study may be considered effective factors for inducing bone formation.",
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Effect of recombinant human bone morphogenetic protein-2, -4, and -7 on bone formation in rat calvarial defects. / Hyun, Suk Ju; Han, Dong Kwan; Choi, Seongho; Chai, Jung Kiu; Cho, Kyoo Sung; Kim, Chong Kwan; Kim, ChangSung.

In: Journal of Periodontology, Vol. 76, No. 10, 01.10.2005, p. 1667-1674.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effect of recombinant human bone morphogenetic protein-2, -4, and -7 on bone formation in rat calvarial defects

AU - Hyun, Suk Ju

AU - Han, Dong Kwan

AU - Choi, Seongho

AU - Chai, Jung Kiu

AU - Cho, Kyoo Sung

AU - Kim, Chong Kwan

AU - Kim, ChangSung

PY - 2005/10/1

Y1 - 2005/10/1

N2 - Background: Currently, more than 20 bone morphogenetic proteins (BMPs) have been identified, and many trials have been carried out using recombinant human BMPs (rhBMPs) for bone tissue engineering. However, comparative analyses on bone formative activities of rhBMP using a preclinical model have been limited. Therefore, the aim of this study was to evaluate and compare the osteogenic potential of rhBMP-2, -4, and -7 delivered with absorbable collagen sponge (ACS) upon early (2 weeks) and complete (8 weeks) wound healing phases in a critical sized rat calvarial defect model. Methods: Eight-millimeter critical sized calvarial defects were created in 30 male Sprague-Dawley rats. The animals were divided into three groups of 10 animals each. The defects were treated with 0.025 mg/ml rhBMP-2/ACS, rhBMP-4/ACS, or rhBMP-7/ACS. The rats were sacrificed at either 2 (five rats) or 8 (five rats) weeks after surgery, and the results were evaluated histologically, histomorphometrically, and immunohistometrically. Results: The surgical implantation of rhBMP-2/ACS, rhBMP-4/ACS, or rhBMP-7/ACS resulted in enhanced local bone formation in the rat calvarial defect model at both 2 and 8 weeks. The amount of defect closure, new bone area, and bone density were similar in the three groups at each time point (P>0.05). In terms of bone density and new bone area, there were statistically significant differences between results obtained at 2 weeks and those obtained at 8 weeks in all groups (P<0.05). Two-way analysis of variance (ANOVA) revealed that there was no correlation between the time and conditions (P>0.05), but time was found to have a strong influence on defect closure, new bone area, and bone density (P<0.05). Irrespective of rhBMP type, positive immunoreactions of osteopontin (OPN) and osteocalcin (OCN) were evident at 2 and 8 weeks. Intense OPN and OCN staining was observed near the newly formed bone as well as in some cells within the new bone. Conclusions: Within the rhBMP types used, rhBMP concentration, and the observation interval, there appears to be no specific differences in bone regenerative potential. All rhBMPs used in this study may be considered effective factors for inducing bone formation.

AB - Background: Currently, more than 20 bone morphogenetic proteins (BMPs) have been identified, and many trials have been carried out using recombinant human BMPs (rhBMPs) for bone tissue engineering. However, comparative analyses on bone formative activities of rhBMP using a preclinical model have been limited. Therefore, the aim of this study was to evaluate and compare the osteogenic potential of rhBMP-2, -4, and -7 delivered with absorbable collagen sponge (ACS) upon early (2 weeks) and complete (8 weeks) wound healing phases in a critical sized rat calvarial defect model. Methods: Eight-millimeter critical sized calvarial defects were created in 30 male Sprague-Dawley rats. The animals were divided into three groups of 10 animals each. The defects were treated with 0.025 mg/ml rhBMP-2/ACS, rhBMP-4/ACS, or rhBMP-7/ACS. The rats were sacrificed at either 2 (five rats) or 8 (five rats) weeks after surgery, and the results were evaluated histologically, histomorphometrically, and immunohistometrically. Results: The surgical implantation of rhBMP-2/ACS, rhBMP-4/ACS, or rhBMP-7/ACS resulted in enhanced local bone formation in the rat calvarial defect model at both 2 and 8 weeks. The amount of defect closure, new bone area, and bone density were similar in the three groups at each time point (P>0.05). In terms of bone density and new bone area, there were statistically significant differences between results obtained at 2 weeks and those obtained at 8 weeks in all groups (P<0.05). Two-way analysis of variance (ANOVA) revealed that there was no correlation between the time and conditions (P>0.05), but time was found to have a strong influence on defect closure, new bone area, and bone density (P<0.05). Irrespective of rhBMP type, positive immunoreactions of osteopontin (OPN) and osteocalcin (OCN) were evident at 2 and 8 weeks. Intense OPN and OCN staining was observed near the newly formed bone as well as in some cells within the new bone. Conclusions: Within the rhBMP types used, rhBMP concentration, and the observation interval, there appears to be no specific differences in bone regenerative potential. All rhBMPs used in this study may be considered effective factors for inducing bone formation.

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