Effects of recombinant human bone morphogenetic protein-2 on differentiation of cells isolated from human bone, muscle, and skin

Kawasaki, Kojiro; Aihara, Masahiko; Honmo, J.; Sakurai, Shunsuke; Fujimaki, Yoshimasa; Sakamoto, Kei; Fujimaki, Etsuo; Wozney, John M.; Yamaguchi, Akira

doi:10.1016/s8756-3282(98)00105-7

Cited by 68 publications

(43 citation statements)

References 33 publications

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“…rhBMP-2 has no effect on CD 2ϩ cells (P Ͼ 0.05). In all studies an increase in cell proliferation in the rhBMP-2 treated cell cultures is reported (2,10,11,12). These results are in line with our findings about the effects of rhBMP-2 on bone marrow cell cultures.…”

Section: Discussionsupporting

confidence: 90%

“…The endpoints measured in those studies were often changes in the level of type I collagen, osteocalcin or alkaline phosphatase (1,2,4,14). Moreover studies of rhBMP-2 in tissues other than bone marrow, such as cells isolated from muscle and skin also showed that rhBMP-2 is able to induce osteoblast differentiation (4,10,15). These findings strongly indicate that there must be cells other than the osteoblast precursor cells that are affected by rhBMP-2.…”

Section: Discussionmentioning

confidence: 99%

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Cell Differentiation under the Influence of rh-BMP-2

Wilke

Traub

Kienapfel

et al. 2001

Biochemical and Biophysical Research Communications

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Cell Differentiation under the Influence of rh-BMP-2

Wilke

Traub

Kienapfel

et al. 2001

Biochemical and Biophysical Research Communications

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“…Relative to n-Bone% in the OCP group in week 8, n-Bone% with OCP/BMP was approximately 194 -224%, whereas that with OCP/ TGF-␤ 1 was only 122%. It is generally accepted that rhBMP-2 conducts stem cells to the osteoblastic lineage, 22,23 whereas TGF-␤ 1 has a stimulatory effect on already committed osteoblasts, but not on stem cells. 24 BMP-2 may recruit more cells that are available for bone regeneration than TGF-␤ 1 .…”

Section: Discussionmentioning

confidence: 99%

New scaffold for recombinant human bone morphogenetic protein‐2

Kamakura

Nakajo

Сузукі

et al. 2004

J Biomedical Materials Res

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A bioactive and resorbable scaffold is necessary to exhibit the osteoinductive potency of recombinant human bone morphogenetic protein-2 (rhBMP-2). In a previous study, we found that synthetic octacalcium phosphate (OCP) enhances bone regeneration and is replaced by newly formed bone after it is resorbed. We hypothesized that OCP may be useful as an effective scaffold for rhBMP-2 to enhance bone regeneration. To test this hypothesis, the present study was designed to investigate whether an OCP/BMP composite implant could more effectively enhance bone regeneration. A critical-sized defect was made in a rat calvarium and 1. 15 mg of OCP combined with 10 microg of rhBMP-2 (OCP/BMP 10 microg), 2. 15 mg of OCP combined with 1 microg of rhBMP-2 (OCP/BMP 1 microg), or 3. OCP (OCP alone) was implanted into the defect and fixed at 4 or 8 weeks after implantation. The percentage of newly formed bone (n-Bone%) in the defect was determined by a histomorphometrical analysis. A statistical analysis showed that n-Bone% with OCP/BMP was significantly higher than that with OCP at both time points, whereas the difference in n-Bone% between OCP/BMP 10 microg and OCP/BMP 1 microg was not significant. The present results suggest that OCP can be used as an effective scaffold for rhBMP-2 and this OCP delivery system may be able to reduce the standard effective dose of rhBMP-2, which would be beneficial because low doses (<100 microg/g OCP) of rhBMP-2 enhance bone regeneration.

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“…8 In vitro experiments, using recombinant human BMP-2 (rhBMP-2) have been carried out to explore the effects of BMPs on the differentiation of osteoblasts and the formation of bone. [9][10][11][12] A sequence analysis of the amino-acid composition of human BMP-4 and BMP-4 derived from Xenopus laevis (rxBMP-4) has revealed a close relationship between both proteins, especially in the mature part of the protein. 13 To the best of our knowledge, nothing is known about the physiological effects of rxBMP-4 on the process of differentiation and repair of human bones, but it is known to be an inducer of mesoderm formation during the early stage of development of the Xenopus embryo 13 and it provokes cell differentiation of the osteoblastic mouse cell line MC3T3-E1.…”

mentioning

confidence: 99%

BMP-4 of Xenopus laevis stimulates differentiation of human primary osteoblast-like cells

Mayr-Wohlfart

Kessler

Puhl

et al. 2001

The Journal of Bone and Joint Surgery. British volume

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Since bone morphogenetic proteins (BMPs) are highly homologous, we investigated the hypothesis that recombinant BMP-4 of the genome of Xenopus laevis (rxBMP-4) may influence the proliferation or differentiation of human primary osteoblast-like cells (HPOC), as occurs with recombinant human BMP (rhBMP-2).HPOC were incubated in the presence of either rxBMP-4, rhBMP-2 or basic fibroblast growth factor (rh-bFGF). The last two were used as positive controls and are known to induce differentiation or proliferation of HPOC, respectively. rxBMP-4 (50 ng/ml and 100 ng/ml) induced a differentiation of HPOC to almost the same extent as rhBMP-2, whereas the addition of rh-bFGF, applied in the same concentration, failed to have any influence on cell differentiation. rh-bFGF however, provoked an increase in cell proliferation of up to 150% when compared with non-stimulated HPOC, while rhBMP-2 and rxBMP-4 had no such effect.Our results indicate an equipotent effect of rhBMP-2 and rxBMP-4 obtained from Xenopus laevis on the differentiation and proliferation of human primary osteoblast-like cells. this superfamily. BMP-2 has been shown to induce bone formation de novo and bone repair in vivo. 8 In vitro experiments, using recombinant human BMP-2 (rhBMP-2) have been carried out to explore the effects of BMPs on the differentiation of osteoblasts and the formation of bone. 9-12A sequence analysis of the amino-acid composition of human BMP-4 and BMP-4 derived from Xenopus laevis (rxBMP-4) has revealed a close relationship between both proteins, especially in the mature part of the protein. 13 To the best of our knowledge, nothing is known about the physiological effects of rxBMP-4 on the process of differentiation and repair of human bones, but it is known to be an inducer of mesoderm formation during the early stage of development of the Xenopus embryo 13 and it provokes cell differentiation of the osteoblastic mouse cell line MC3T3-E1.14 Because of the high conservation and the similarity of the protein, the question arose as to whether rxBMP-4 like rhBMP-2 is able to promote the differentiation of human osteoblasts. To test this hypothesis, we examined the effects of rxBMP-4, rhBMP-2 and recombinant human fibroblast growth factor (rh-bFGF). In contrast to BMPs, bFGF, which is also synthesised in osteoblasts, seems to be a bone-regulating factor since it enhances the proliferation of osteoblasts in vitro 15,16 with an inhibitory effect on their differentiation. 17 Materials and MethodsCell culture. Cultures of osteoblasts were established according to the method described by Robey and Termine. 18 Fragments of cancellous bone were obtained during routine hip and knee replacements from four men and two women aged between 34 and 79 years. The fragments were dissected, minced, and rinsed several times with physiological saline solution to remove blood components. For collagenase digestion, the bone chips were incubated in serum-free Dulbecco's modification of Eagle's minimum

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Effects of recombinant human bone morphogenetic protein-2 on differentiation of cells isolated from human bone, muscle, and skin

Cited by 68 publications

References 33 publications

Cell Differentiation under the Influence of rh-BMP-2

Cell Differentiation under the Influence of rh-BMP-2

New scaffold for recombinant human bone morphogenetic protein‐2

BMP-4 of Xenopus laevis stimulates differentiation of human primary osteoblast-like cells

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