Bone Induction by BMPs/OPs and Related Family Members in Primates

Ripamonti, Ugo; Ramoshebi, Lentsha Nathaniel; Matsaba, Thato; Tasker, Jacqueline; Crooks, Jean; Teare, June

doi:10.2106/00004623-200100002-00006

Cited by 48 publications

(128 citation statements)

References 39 publications

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“…[25][26][27] In addition to the direct application of recombinant BMP proteins, numerous reports have confirmed the ability of adenoviral or retroviral vector-mediated gene transfer of several BMPs to induce bone formation in animal models. 18,20,21,23,[28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] Although a plethora of studies have demonstrated the ability of several BMPs, mostly BMP-2 and BMP-7, to promote osteogenesis, it is unclear whether or not BMPs other than those currently being tested in clinical trials are more potent stimulators of new bone formation. Thus, it is important to conduct a comprehensive comparative analysis of the in vivo osteogenic activity of all BMPs.…”

Section: Introductionmentioning

confidence: 99%

Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery

et al. 2004

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Efficacious bone regeneration could revolutionize the clinical management of bone and musculoskeletal disorders. Although several bone morphogenetic proteins (BMPs) (mostly BMP-2 and BMP-7) have been shown to induce bone formation, it is unclear whether the currently used BMPs represent the most osteogenic ones. Until recently, comprehensive analysis of osteogenic activity of all BMPs has been hampered by the fact that recombinant proteins are either not biologically active or not available for all BMPs. In this study, we used recombinant adenoviruses expressing the 14 types of BMPs (AdBMPs), and demonstrated that, in addition to currently used BMP-2 and BMP-7, BMP-6 and BMP-9 effectively induced orthotopic ossification when either AdBMP-transduced osteoblast progenitors or the viral vectors were injected into the quadriceps of athymic mice. Radiographic and histological evaluation demonstrated that BMP-6 and BMP-9 induced the most robust and mature ossification at multiple time points. BMP-3, a negative regulator of bone formation, was shown to effectively inhibit orthotopic ossification induced by BMP-2, BMP-6, and BMP-7. However, BMP-3 exerted no inhibitory effect on BMP-9-induced bone formation, suggesting that BMP-9 may transduce osteogenic signaling differently. Our findings suggest that BMP-6 and BMP-9 may represent more effective osteogenic factors for bone regeneration.

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Section: Introductionmentioning

confidence: 99%

Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery

et al. 2004

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“…The BMPs/OPs are a family of highly conserved secreted pleiotropic proteins that initiate cartilage and bone formation in vivo [1][2][3][4][5][6][7] BMPs/OPs are members of the transforming growth factor-β (TGF-β) superfamily and play critical roles as soluble mediators of tissue morphogenesis [1][2][3][4][5][6][7][8][9]. In addition to post-natal osteogenesis, BMPs/OPs play multiple roles in embryonic development and are involved in inductive events unrelated to bone induction that control pattern formation during embryonic organogenesis [2][3][4][5][6][7][8][9].…”

mentioning

confidence: 99%

“…In addition to post-natal osteogenesis, BMPs/OPs play multiple roles in embryonic development and are involved in inductive events unrelated to bone induction that control pattern formation during embryonic organogenesis [2][3][4][5][6][7][8][9].…”

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confidence: 99%

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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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“…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. However, the allografts used in this study were deep-frozen directly after harvesting and prepared while adding an antibiotic solution.…”

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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Bone Induction by BMPs/OPs and Related Family Members in Primates

Cited by 48 publications

References 39 publications

Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery

Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery

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

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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