A Bovine Low Molecular Weight Bone Morphogenetic Protein (BMP) Fraction

Urist, Marshall R.; Lietze, Arthur; Mizutani, Hideki; Takagi, Katsumasa; Triffitt, James T.; Amstutz, Julie; DeLange, Robert J.; Termine, John D.; Finerman, Gerald A. M.

doi:10.1097/00003086-198201000-00037

Cited by 149 publications

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“…A physical interaction between BMP-2 and heparin could be seen in biosensor experiments, where BMP-2 bound to immobilized heparin with a dissociation constant, Kd, of approximately 20 nM, whereas the heparin-binding of variant EHBMP-2 was negligible. These results identify the basic N-terminal domains of dimeric BMP-2 as heparin-binding sites that are not obligatory for receptor activation but modulate its biological activity.Keywords: human bone morphogenetic protein ; bacterial expression ; heparin binding; limb bud; proteoglycan synthesis ; variant bone morphogenetic protein 2.Bone morphogenetic protein 2 (BMP-2) is one of the proteins originally identified as factors extractable from bone and triggering ectopic bone formation at non-skeletal sites in vivo (Urist, 1965;Sampath and Reddi, 1981;Urist et al, 1982; for review see Wozney, 1992;Rosen and Thies, 1992;Reddi, 1994). After cloning and expression in Chinese hamster ovary (CHO) cells Wang et al, 1990) purified BMP-2 has been established to induce de novo bone formation and bone repair in adult animals (see, for example, Toriumi et al, 1991), and chondrogenic and osteogenic differentiation in various cellular systems in vitro.…”

mentioning

confidence: 99%

Human Bone Morphogenetic Protein 2 Contains a Heparin‐Binding Site which Modifies Its Biological Activity

Ruppert

Hoffmann

Sebald

1996

European Journal of Biochemistry

523

444

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Bone morphogenetic protein 2 (BMP-2) plays a decisive role during bone regeneration and repair as well as during various stages of embryonal development. A cDNA encoding mature human BMP-2 could be efficiently expressed in Esclzerichia coli, and after renaturation a dimeric BMP-2 protein of M , 26000 was prepared with a purity greater 98 %. The recombinant BMP-2 was functionally active as demonstrated by the induction of alkaline phosphatase activity in the C3HlOT1/2 fibroblast cell line (EC,, of 70 nM) and proteoglycan synthesis in embryonic chicken limb bud cells (EC,,(15)(16)(17)(18)(19)(20). A peptide 1-17 representing the N-terminal basic part of BMP-2 as well as heparin increased the specific activity of the protein about fivefold in the limb bud assay. These observations suggested that the N-termini reduce the specific activity of BMP-2, probably by interacting with heparinic sites in the extracellular matrix. This conclusion was supported by a variant EHBMP-2, where the N-terminal residues 1-12 of BMP-2 had been substituted by a dummy sequence of equal length and which showed an EC,, value of around 1 nM which was affected neither by heparin nor by peptide 1 -17. A physical interaction between BMP-2 and heparin could be seen in biosensor experiments, where BMP-2 bound to immobilized heparin with a dissociation constant, Kd, of approximately 20 nM, whereas the heparin-binding of variant EHBMP-2 was negligible. These results identify the basic N-terminal domains of dimeric BMP-2 as heparin-binding sites that are not obligatory for receptor activation but modulate its biological activity.Keywords: human bone morphogenetic protein ; bacterial expression ; heparin binding; limb bud; proteoglycan synthesis ; variant bone morphogenetic protein 2.Bone morphogenetic protein 2 (BMP-2) is one of the proteins originally identified as factors extractable from bone and triggering ectopic bone formation at non-skeletal sites in vivo (Urist, 1965;Sampath and Reddi, 1981;Urist et al., 1982; for review see Wozney, 1992;Rosen and Thies, 1992;Reddi, 1994). After cloning and expression in Chinese hamster ovary (CHO) cells Wang et al., 1990) purified BMP-2 has been established to induce de novo bone formation and bone repair in adult animals (see, for example, Toriumi et al., 1991), and chondrogenic and osteogenic differentiation in various cellular systems in vitro. In addition, BMP-2 regulates, similarly to its nearest homologue BMP-4, diverse fundamental processes during embryonic development (see, for example, Kingsley, 1994). The mature BMP-2 protein is closely related to the Drosophila dpp protein (Padgett et al., 1993) and the Xenopus BMP-2 (Plessow et al., 1991). The human BMP-2 can substitute the Drosophila homologue dpp during dorsalventral patterning, and, vice versa, a recombinant dpp protein induces ectopic bone formation in rats (Padgett et al., 1993;Sampath et al., 1993). BMP-2 and the other BMP have great potential for medical therapeutic applications, in particular beCorrespondence to W. Sebald, Physiologisc...

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mentioning

confidence: 99%

Human Bone Morphogenetic Protein 2 Contains a Heparin‐Binding Site which Modifies Its Biological Activity

Ruppert

Hoffmann

Sebald

1996

European Journal of Biochemistry

523

444

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“…decalcification exposes on its surface, the bone morphogenetic proteins (BMPs) which are osteoinductive [5][6][7][8][9][10][11] that is, they induce differentiation of mesenchymal cells into cartilage and bone [12]. BMPs are natural proteins which play important roles during embryogenesis and mediate in specific aspects of skeletal growth and development during later adult life [13].…”

Section: Discussionmentioning

confidence: 99%

A Comparative Evaluation of Decalcified Freeze Dried Bone Allograft, Hydroxyapatite and Their Combination in Osseous Defects of the Jaws

Mishra

Singh

Mohammad

et al. 2010

J. Maxillofac. Oral Surg.

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Objectives To evaluate decalcified freeze dried allograft or hydroxyapatite and a combination of both as bone autograft substitutes in the healing of osseous jaw defects. Materials and Methods 24 patients participated in the study which involved the filling of osseous defects in the maxilla/mandible with decalcified freeze dried bone allograft (DFDBA) or hydroxyapatite (HA) or a combined graft composed of these two in equal proportions. Results Bone formation occurred as early as 4 weeks in the DFDBA and combination groups and 12 weeks in the HA group which was verified by radiographs, Dentascans (DentaScanÒ Software Program, General Electric, USA) and bone scintigraphy. Conclusion Both these materials can be used as bone graft substitutes in smaller defects although their suitability in large defects is yet to be studied.

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“…After an effective delipidation process using organic solvents, the bovine bone is treated twice with 8M urea to extract proteins (Chappard et al 1993). Treatment with urea extracts bone morphogenetic proteins (BMP) (Urist et al 1982). BMPs can induce bone formation in primates (Ripamonti et al 2001) and a lack of BMPs in substitute materials could reduce stimulation of bone formation.…”

Section: Discussionmentioning

confidence: 99%

Faster integration of human allograft bone than of the bovine substitute LubbocNon-randomized evaluation of 20 cases with benign tumors or tumorlike conditions

Hartl

Bitzan

Wanivenhaus

et al. 2004

Acta Orthopaedica Scandinavica

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A Bovine Low Molecular Weight Bone Morphogenetic Protein (BMP) Fraction

Cited by 149 publications

References 0 publications

Human Bone Morphogenetic Protein 2 Contains a Heparin‐Binding Site which Modifies Its Biological Activity

Human Bone Morphogenetic Protein 2 Contains a Heparin‐Binding Site which Modifies Its Biological Activity

A Comparative Evaluation of Decalcified Freeze Dried Bone Allograft, Hydroxyapatite and Their Combination in Osseous Defects of the Jaws

Faster integration of human allograft bone than of the bovine substitute LubbocNon-randomized evaluation of 20 cases with benign tumors or tumorlike conditions

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