Bone Morphogenesis in Implants of Insoluble Bone Gelatin

Urist, Marshall R.; Iwata, Hiroji; Ceccotti, Peter L.; Dorfman, Robert L.; Boyd, Stuart D.; McDowell, Richard; Chien, Constance

doi:10.1073/pnas.70.12.3511

Cited by 214 publications

(86 citation statements)

References 25 publications

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“…This process was known as demineralization, and the obtained tissue is referred as demineralized bone. 22 The proteins were then extracted by incubation of demineralized bone slices in denaturing buffer of 6 M guanidine-HCl and 100 mM Tris (pH 7.4). For comparison, the undemineralized bone slices were also incubated in the same denaturing buffer for extraction of proteins.…”

Section: Resultsmentioning

confidence: 99%

Method Development of Efficient Protein Extraction in Bone Tissue for Proteome Analysis

et al. 2007

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Exploring bone proteome is an important and challenging task for understanding the mechanisms of physiological/pathological process of bone tissue. However, classical methods of protein extraction for soft tissues and cells are not applicable for bone tissue. Therefore, method development of efficient protein extraction is critical for bone proteome analysis. We found in this study that the protein extraction efficiency was improved significantly when bone tissue was demineralized by hydrochloric acid (HCl). A sequential protein extraction method was developed for large-scale proteome analysis of bone tissue. The bone tissue was first demineralized by HCl solution and then extracted using three different lysis buffers. As large amounts of acid soluble proteins also presented in the HCl solution, besides collection of proteins in the extracted lysis buffers, the proteins in the demineralized HCl solution were also collected for proteome analysis. Automated 2D-LC-MS/MS analysis of the collected protein fractions resulted in the identification of 6202 unique peptides which matched 2479 unique proteins. The identified proteins revealed a broad diversity in the protein identity and function. More than 40 bone-specific proteins and 15 potential protein biomarkers previously reported were observed in this study. It was demonstrated that the developed extraction method of proteins in bone tissue, which was also the first large-scale proteomic study of bone, was very efficient for comprehensive analysis of bone proteome and might be helpful for clarifying the mechanisms of bone diseases.

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Section: Resultsmentioning

confidence: 99%

Method Development of Efficient Protein Extraction in Bone Tissue for Proteome Analysis

et al. 2007

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“…TGFβ-like BMPs play a broad range of roles in processes that include dorsal/ventral patterning, organogenesis, neural development (Hogan, 1996;Furuta et al, 1997;De Robertis and Kuroda, 2004), and osteogenesis (Urist et al, 1973;Wozney et al, 1988). In particular, signaling gradients of BMP2 and BMP4 in vertebrates, and of the Drosophila orthologue decapentaplegic (DPP), are the major determinants for forming the dorsal-ventral axis in gastrulation (Hogan, 1996).…”

Section: Bmps 2 Andmentioning

confidence: 99%

“…In seminal work, Urist and colleagues demonstrated that protein factor(s) from demineralized bone extracts could induce ectopic bone formation (Urist, 1965;Urist et al, 1973) via a process recapitulating the endochondral bone formation of normal development (Reddi and Huggins, 1972). These factor(s) were designated bone morphogenetic protein (BMP) (Urist et al, 1973), and extensive purification of bone inductive activity from bone extracts led to initial isolation of BMPs 1-7 (Celeste et al, 1990;Wang et al, 1988;Wozney et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

“…These factor(s) were designated bone morphogenetic protein (BMP) (Urist et al, 1973), and extensive purification of bone inductive activity from bone extracts led to initial isolation of BMPs 1-7 (Celeste et al, 1990;Wang et al, 1988;Wozney et al, 1988). BMPs 2-7 are members of the TGFβ superfamily of proteins, and over 30 TGFβ-like BMPs have now been identified, primarily via sequence homology, in a broad range of species (Hogan, 1996;Ducy and Karsenty, 2000).…”

Section: Introductionmentioning

confidence: 99%

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The bone morphogenetic protein 1/Tolloid-like metalloproteinases

2007

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A decade ago, bone morphogenetic protein 1 (BMP1) was shown to provide the activity necessary for proteolytic removal of the C-propeptides of procollagens I-III: precursors of the major fibrillar collagens. Subsequent studies have shown BMP1 to be the prototype of a small group of extracellular metalloproteinases that play manifold roles in regulating formation of the extracellular matrix (ECM). Soon after initial cloning of BMP1, genetic studies showed the related Drosophila proteinase Tolloid (TLD) to be necessary for formation of the dorsal-ventral axis in early embryogenesis. It is now clear that the BMP1/TLD-like proteinases, conserved in species ranging from Drosophila to humans, act in dorsal-ventral patterning via activation of transforming growth factor β (TGFβ)-like proteins BMP2, BMP4 (vertebrates) and decapentaplegic (arthropods). More recently, it has become apparent that the BMP1/TLD-like proteinases are key activators of a broader subset of the TGFβ superfamily of proteins, with implications that these proteinases may be key in orchestrating formation of ECM with growth factor activation and BMP signaling in morphogenetic processes.

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“…BMP was first postulated by Urist in 1965 [23], and was subsequently extracted chemically from demineralized bone matrix [17,24]. Wozney et al [27] employed recombinant DNA technology to produce the proteins in 1988.…”

Section: Methodsmentioning

confidence: 99%

Repair of Ulnar Segmental Defect by Recombinant Human Bone Morphogenetic Protein-2 in Dogs.

Itoh

Mochizuki

Nishimura

et al. 1998

The Journal of Veterinary Medical Science

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ABSTRACT. The efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2) combined with poly D, L lactic-co-glycolic acid (PLGA)/gelatin sponge complex (PGS) as a carrier on the repair of segmental long-bone defects was evaluated using an ulnar model in dogs. The defect was 2 cm in length and was fixed with bone plating. After implantation of PGS with or without rhBMP-2, the repair process of the defect was evaluated by serial radiography until 16 postoperative weeks. All defects treated with 160 µg or 640 µg of rhBMP-2/PGS revealed bone union radiographically by 12 postoperative weeks, whereas all defects treated with PGS alone revealed no radiographic evidence of healing throughout the experimental period. In defects treated with 40 µg of rhBMP-2/PGS, new bone appeared partially at the defects but did not accomplish union. Bone mineral contents at the defect sites after harvest at 16 weeks postoperatively were significantly (p<0.05) higher in those treated with 160 µg or 640 µg of rhBMP-2 than in those treated with 40 µg of rhBMP-2 or PGS alone. Histologically, defects radiographically diagnosed as having achieved union showed the appearance of cortical bone and bone marrow cells. These findings suggest the use of rhBMP-2/PGS as a potential bone graft substitute in reconstructive surgery in dogs. -KEY WORDS: canine, rhBMP-2, ulnar defect.

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Bone Morphogenesis in Implants of Insoluble Bone Gelatin

Cited by 214 publications

References 25 publications

Method Development of Efficient Protein Extraction in Bone Tissue for Proteome Analysis

Method Development of Efficient Protein Extraction in Bone Tissue for Proteome Analysis

The bone morphogenetic protein 1/Tolloid-like metalloproteinases

Repair of Ulnar Segmental Defect by Recombinant Human Bone Morphogenetic Protein-2 in Dogs.

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