Initiation of Bone Regeneration in Adult Baboons by Osteogenin, a Bone Morphogenetic Protein

Ripamonti, Ugo; Ma, Shuhua; Cunningham, Nicholas; Yeates, Laura; Reddi, A. Hari

doi:10.1016/s0934-8832(11)80033-8

Cited by 98 publications

(54 citation statements)

References 34 publications

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“…The heterotopic and orthotopic calvarial models of tissue induction and morphogenesis by naturallyderived and recombinant proteins in the adult baboon Papio ursinus have been described in detail [8,13,22,[24][25][26]. Implants for heterotopic implantation in the rectus abdominis were prepared in sterile 10 ml polypropylene tubes by adding 0, 10, 50 and 250µg of hOP-1 in 100µl of liquid vehicle to 100 mg of bovine insoluble collagenous matrix.…”

Section: Primate Models For Tissue Inductionmentioning

confidence: 99%

Bone induction by recombinant human osteogenic protein-1 (hOP-1, BMP-7) in the primate Papio ursinus with expression of mRNA of gene products of the TGF-? superfamily

Ripamonti

2005

J Cellular Mol Med

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Predictable bone induction in clinical contexts requires information on the expression and cross regulation of gene products of the transforming growth factor‐β (TGF‐β) superfamily elicited by single applications of each recombinant human bone morphogenetic/ostegenic proteins (BMPs/OPs). Using the calvarium and the rectus abdominis muscle of adult baboons Papio ursinus as a model for tissue induction and morphogenesis, this study investigated the induction of bone morphogenesis by γ‐irradiated hOP‐1 delivered by γ‐irradiated bovine insoluble collagenous bone matrix, the hOP‐1 osteogenic device, for bone induction in heterotopic and orthotopic sites of the primate Papio ursinus and the expression patterns of OP‐1, collagen type IV, BMP‐3 and TGFβ1mRNAs elicited by increasing single applications of doses of the hOP‐1 osteogenic devices (0.1, 0.5 and 2.5 mg hOP‐1/g of matrix) applied heterotopically in the rectus abdominis muscle and orthotopically in 48 calvarial defects of 12 adult baboons. Histology and histomorphometry on serial undecalcified sections prepared from the specimens harvested on day 15, 30 and 90 showed that all the doses of the hOP‐1 osteogenic device induced bone formation culminating in complete calvarial regeneration by day 90. Type IV collagen mRNA expression, a marker of angiogenesis, was strongly expressed in both heterotopic and orthotopic tissues. High levels of expression of OP‐1 mRNA demonstrated autoinduction of OP‐1 mRNAs. Expression levels of BMP‐3 mRNA varied from tissues induced in heterotopic vs. orthotopic sites with high expression in rapidly forming heterotopic ossicles together with high expression of type IV collagen mRNA. The temporal and spatial expressions of TGF‐β1 mRNA indicate a specific temporal transcriptional window during which expression of TGF‐β1 is mandatory for successful and optimal osteogenesis. The induction of bone by hOP‐1 in Papio ursinus develops as a mosaic structure with distinct spatial and temporal patterns of gene expression of members of the TGF‐β superfamily that singly, synergistically and synchronously initiate and maintain tissue induction and morphogenesis.

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Section: Primate Models For Tissue Inductionmentioning

confidence: 99%

Bone induction by recombinant human osteogenic protein-1 (hOP-1, BMP-7) in the primate Papio ursinus with expression of mRNA of gene products of the TGF-? superfamily

Ripamonti

2005

J Cellular Mol Med

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“…Identified BMPs include BMP 2 -BMP 7 and are currently being investigated for possible clinical use in the repair of bone defects or trauma [26]. The BMPs have received much attention due to their ability to promote bone formation in vitro and in vivo [105][106][107][108][109]. For example, implantation of 0.5 -115 µg of recombinant human BMP-2 induced ectopic bone formation in rats [110].…”

Section: Osteoinductive Bone Scaffoldsmentioning

confidence: 99%

Osteoblast response to zirconia‐hybridized pyrophosphate‐stabilized amorphous calcium phosphate

Whited

Škrtić

Love

et al. 2005

J Biomedical Materials Res

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(Abstract)Biodegradable polyesters, such as poly(DL-lactic-co-glycolic acid) (PLGA), have been used to fabricate porous bone scaffolds to support bone tissue development. These scaffolds allow for cell seeding, attachment, growth and extracellular matrix production in vitro and are replaced by new bone tissue when implanted into bone sites in vivo.Hydroxyapatite (HAP) and β-tricalcium phosphate (β-TCP) ceramics have been incorporated into PLGA bone scaffolds and have been shown to increase their osteoconductivity (support cell attachment). Although HAP, β-TCP, and biodegradable polyesters are osteoconductive, there is no evidence that these scaffold materials are osteoinductive (support cell differentiation). Calcium and phosphate ions, in contrast, have been postulated to be osteogenic factors that enhance osteoblast differentiation and mineralization. Recently, a zirconia-hybridized pyrophosphate stabilized amorphous calcium phosphate (Zr-ACP) has been synthesized which permits controlled release of calcium and phosphate ions and thus is hypothesized to be osteoinductive. Incorporation of Zr-ACP into a highly porous poly(DL lactic-co-glycolic acid) (PLGA) scaffold could potentially increase the osteoinductivity of the scaffold and therefore promote osteogenesis when implanted in vivo.To determine the osteoinductivity of Zr-ACP, a MC3T3-E1 mouse calvarialderived osteoprogenitor cell line was used to measure cell response to Zr-ACP. To accomplish this objective, Zr-ACP was added to cell culture at different stages in cell maturation (days 0, 4 and 11). DNA synthesis, alkaline phosphatase (ALP) activity, iii osteopontin synthesis and collagen synthesis were determined. Results indicate that culture in the presence of Zr-ACP significantly increased cell proliferation, ALP activity and osteopontin synthesis but not collagen synthesis. To determine the feasibility of incorporating Zr-ACP into a PLGA scaffold, PLGA/Zr-ACP composite foams (5% or 10% (w/v) polymer:solvent with 25 wt% or 50 wt% Zr-ACP) were fabricated using a thermal phase inversion technique. Scanning electron microscopy revealed a highly porous structure with pores ranging in size from a few microns to about 100 µm. The amorphous structure of the Zr-ACP was maintained during composite fabrication as confirmed by X-ray diffraction measurements. Composite scaffolds also showed significantly greater compressive yield strengths and moduli as compared to pure polymer scaffolds.The results of this study indicate that Zr-ACP enhances the osteoblastic phenotype of MC3T3-E1 cells in vitro and can be incorporated into a porous PLGA scaffold. Porous PLGA/Zr-ACP composites are promising for use as bone scaffolds to heal bone defects.iv

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“…Bone morphogenetic proteins BMP-2, BMP-3 (osteogenin), BMP-4, BMP-5, BMP-6 (Vg-1). osteogenic protein-1 (OP-1; BMP-7), and osteogenic protein-2 (BMP-8) have been implicated in cartilage and bone formation both in vitro and in vivo (3, 15,22,23,[27][28][29][30]34,36,38,42). There is accumulating evidence that morphogenetic proteins are important regulators of many morphogenetic events during embryogenesis.…”

Section: Introductionmentioning

confidence: 99%

Expression pattern of osteogenic protein-1 (bone morphogenetic protein-7) in human and mouse development.

Helder¹,

Özkaynak²,

Sampath³

et al. 1995

J Histochem Cytochem.

175

114

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Osteogenic protein-1 (OM; BMP7) is a member of the bone morphogenetic protein subfamily. Because members of the TGF-p superfamily have a role in tissue development, the distribution of OP1 expression in developing human embryos (5-8 gestational weeks) and fetuses (8-14 gestational weeks) and mouse (9.5-17.5 gestational days) fetuses was examined. Northern hybridization with specific OB1 probes revealed two mRNA species of 4 and 2.2 KFI. Highest levels of OP1 mRNA were found in human fetal kidney and heart between 12-14 weeks of gestation. By in situ hybridization, the OP-1 transcripts were found in various tissues, i.e., the ectodermal epithelium of the mouse fore-and hindlimbs, heart, teeth, intestinal epithelium, perichondrium, hyper-

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Initiation of Bone Regeneration in Adult Baboons by Osteogenin, a Bone Morphogenetic Protein

Cited by 98 publications

References 34 publications

Bone induction by recombinant human osteogenic protein-1 (hOP-1, BMP-7) in the primate Papio ursinus with expression of mRNA of gene products of the TGF-? superfamily

Bone induction by recombinant human osteogenic protein-1 (hOP-1, BMP-7) in the primate Papio ursinus with expression of mRNA of gene products of the TGF-? superfamily

Osteoblast response to zirconia‐hybridized pyrophosphate‐stabilized amorphous calcium phosphate

Expression pattern of osteogenic protein-1 (bone morphogenetic protein-7) in human and mouse development.

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