Transforming Growth Factor-β2 Enhances the Osteoinductive Activity of a Bovine Bone-Derived Fraction Containing Bone Morphogenetic Protein-2 and 3

Bentz, Hanne; Thompson, Andrea Y.; Armstrong, R. M.; Chang, Ray-Jen; Piez, Karl A.; Rosen, David

doi:10.1016/s0934-8832(11)80234-9

Cited by 71 publications

(23 citation statements)

References 25 publications

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“…42,43 In several studies attempts were made to enhance bone regeneration by combining TGF-b and BMPs (Table 2). [42][43][44][45][46][47][48][49][50] To investigate a possible interaction between TGF-b and BMP during bone induction, the combination was always compared to similar dosages of each of the individual growth factor. Despite the differences in experimental settings, isoforms used and delivery vehicles, most studies showed an additive or synergistic effect of the combination.…”

Section: Bmps and Their Combinationsmentioning

confidence: 99%

Growth Factor Interactions in Bone Regeneration

Kempen

Creemers

Alblas

et al. 2010

Tissue Engineering Part B: Reviews

100

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Bone regeneration is a complex process regulated by a large number of bioactive molecules. Many growth factors and cytokines involved in the natural process of bone healing have been identified and tested as potential therapeutic candidates to enhance the regeneration process. Although many of these studies show an enhancement of the bone regeneration process by a single drug therapy, in vivo bone regeneration is the result of a complex interplay between the applied growth factor and various endogenous produced growth factors. To investigate these growth factor interactions, various studies have investigated the effect of growth factor combinations on bone regeneration. This review provides an overview of the growth factor and cytokine combinations tested in translational bone regeneration studies and shows that their interaction may result in an enhancement or inhibition of bone formation.

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Section: Bmps and Their Combinationsmentioning

confidence: 99%

Growth Factor Interactions in Bone Regeneration

Kempen

Creemers

Alblas

et al. 2010

Tissue Engineering Part B: Reviews

100

View full text Add to dashboard Cite

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“…It can be extracted after demineralisation of the bone by chaotropic agents; it has been purified to near homogeneity Luyten et al, 1989;Bentz et al, 1991). Similarly, a BMP-2 has been recovered from Xenopus Zaevis embryos in partially purified form (Shoda et al, 1994).…”

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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“…They include another keratan sulfate-containing proteoglycan, fibromodulin, and the dermatan sulfate proteoglycans decorin biglycan, and epiphycan (9). A seventh member of the family, isolated from bone, was originally called osteoinductive factor and later renamed osteoglycin (10,11). The deduced amino acid sequence obtained from the cDNA of this gene suggests it is potentially a proteoglycan and a member of the SLRP family (12).…”

mentioning

confidence: 99%

Mimecan, the 25-kDa Corneal Keratan Sulfate Proteoglycan, Is a Product of the Gene Producing Osteoglycin

Funderburgh

Corpuz

Roth

et al. 1997

Journal of Biological Chemistry

168

126

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Bovine cornea contains three unique keratan sulfate proteoglycans (KSPGs), of which two (lumican and keratocan) have been characterized using molecular cloning. The gene for the third protein (KSPG25) has not been identified. This study examined the relationship between the KSPG25 protein and the gene for osteoglycin, a 12-kDa bone glycoprotein. The N-terminal amino acid sequence of KSPG25 occurs in osteoglycin cDNA cloned from bovine cornea. The osteoglycin amino acid sequence makes up the C-terminal 47% of the deduced sequence of the KSPG25 protein. Antibodies to osteoglycin reacted with intact corneal KSPG, with KSPG25 protein, and with a 36-kDa protein, distinct from lumican and keratocan. KSPG25-related proteins, not modified with keratan sulfate, were also detected in several connective tissues. Northern blot analysis showed mRNA transcripts of 2.4, 2.5, and 2.6 kilobases in numerous tissues with the 2.4-kilobase transcript enriched in ocular tissues. Ribonuclease protection analysis detected several protected KSPG25 mRNA fragments, suggesting alternate splicing of KSPG25 transcripts. We conclude that the full-length translation product of the gene producing osteoglycin is a corneal keratan sulfate proteoglycan, also present in many non-corneal tissues without keratan sulfate chains. The multiple size protein products of this gene appear to result from in situ proteolytic processing and/or alternative splicing of mRNA. The name mimecan is proposed for this gene and its products.The corneal stroma of vertebrate organisms contains a unique class of molecules, corneal keratan sulfate proteoglycans (KSPGs), 1 consisting of several related proteins each bearing keratan sulfate. The specialized nature of corneal proteoglycans was recognized almost 60 years ago with the initial description of keratan sulfate, the most abundant glycosaminoglycan in cornea (1). Corneal keratan sulfate is a highly sulfated, linear polymer of N-acetyllactosamine, linked to asparagine residues in the KSPG core proteins (2). The unusual abundance of keratan sulfate in the cornea and studies of heritable metabolic diseases suggest that the KSPG molecules are essential in maintenance of corneal transparency (3, 4). Understanding the role of the KSPGs in corneal transparency, their interactions with cells and other matrix molecules, and the tissue-specific nature of their biosynthesis requires complete knowledge of their structure. Although we have excellent information regarding the carbohydrate components of the KSPGs, the core proteins as representatives of the primary KSPG gene products are still not fully understood.Research from our laboratory has shown that keratan sulfate is attached to three unique proteins in bovine cornea (5, 6). The cDNAs for two of these proteins, keratocan and lumican (originally designated 37A and 37B), have been cloned and sequenced (7,8). A third 25-kDa KSPG core protein, KSPG25, was recognized as unique from lumican and keratocan, but its primary sequence is not yet known. The deduced amino acid sequence...

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Transforming Growth Factor-β2 Enhances the Osteoinductive Activity of a Bovine Bone-Derived Fraction Containing Bone Morphogenetic Protein-2 and 3

Cited by 71 publications

References 25 publications

Growth Factor Interactions in Bone Regeneration

Growth Factor Interactions in Bone Regeneration

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

Mimecan, the 25-kDa Corneal Keratan Sulfate Proteoglycan, Is a Product of the Gene Producing Osteoglycin

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