CT and Radionuclide Study of BMP-2 Gene Therapy–Induced Bone Formation

Varady, Peter; Li, Jin Zhong; Alden, Tord D.; Kallmes, David F.; Williams, Mark B.; Helm, Gregory A.

doi:10.1016/s1076-6332(03)80307-0

Cited by 21 publications

(15 citation statements)

References 20 publications

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“…Numerous reports have confirmed that adenoviral, retroviral, or recombinant BMP application induces bone formation in animal models, and these osteoinductive properties have led to the use of rhBMPs as a mainstay in clinical bone regeneration [17,19,21,23,[50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66]. In particular, rhBMP2 and rhBMP7 have been extensively used to augment bony healing [12][13][14][15][16][17][18][19][20][21][22][23], and administration of rhBMP 2 or rhBMP 7 leads to better fusion rates than autografts, successful bony union, and minimal associated complications [11,[24][25][67][68][69][70]. Though much attention has been directed to rhBMPs 2 and 7 in bone regeneration, it is unclear whether these are actually the most osteogenic BMPs.…”

Section: Bone Morphogenetic Proteins (Bmps) As Important Bone Formingmentioning

confidence: 99%

“…Several forms of recombinant BMPs (rhBMPs), most notably rhBMP-2 and rhBMP-7, have been tested in clinical trials and are now used as adjunctive therapy in the clinical setting [12][13][14][15][16][17][18][19][20][21][22][23]. Data from these trials suggest that BMP-induced bone formation is at least equivalent to autologous bone-grafting in treatment of non-unions and spinal fusions [24][25].…”

Section: Introductionmentioning

confidence: 99%

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BMP-9 Induced Osteogenic Differentiation of Mesenchymal Stem Cells: Molecular Mechanism and Therapeutic Potential

Luther¹,

Wagner²,

Zhu³

et al. 2011

CGT

149

167

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Promoting osteogenic differentiation and efficacious bone regeneration have the potential to revolutionize the treatment of orthopaedic and musculoskeletal disorders. Mesenchymal Stem Cells (MSCs) are bone marrow progenitor cells that have the capacity to differentiate along osteogenic, chondrogenic, myogenic, and adipogenic lineages. Differentiation along these lineages is a tightly controlled process that is in part regulated by the Bone Morphogenetic Proteins (BMPs). BMPs 2 and 7 have been approved for clinical use because their osteoinductive properties act as an adjunctive treatment to surgeries where bone healing is compromised. BMP-9 is one of the least studied BMPs, and recent in vitro and in vivo studies have identified BMP-9 as a potent inducer of osteogenic differentiation in MSCs. BMP-9 exhibits significant molecular cross-talk with the Wnt/ β-catenin and other signaling pathways, and adenoviral expression of BMP-9 in MSCs increases the expression of osteogenic markers and induces trabecular bone and osteiod matrix formation. Furthermore, BMP-9 has been shown to act synergistically in bone formation with other signaling pathways, including Wnt/ β-catenin, IGF, and retinoid signaling pathways. These results suggest that BMP-9 should be explored as an effective bone regeneration agent, especially in combination with adjuvant therapies, for clinical applications such as large segmental bony defects, non-union fractures, and/or spinal fusions.

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Section: Bone Morphogenetic Proteins (Bmps) As Important Bone Formingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

BMP-9 Induced Osteogenic Differentiation of Mesenchymal Stem Cells: Molecular Mechanism and Therapeutic Potential

Luther¹,

Wagner²,

Zhu³

et al. 2011

CGT

149

167

View full text Add to dashboard Cite

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“…The identification of BMPs has generated great interest due to their potential use in bone regeneration. 3 Several recombinant forms of BMPs, mostly rhBMP-2 and rhBMP-7 (a.k.a., OP-1), have been shown to induce bone formation in vivo, [13][14][15][16][17][18][19][20][21][22][23][24] and both rhBMP-2 and rhBMP-7 have been tested in clinical trials. [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.…”

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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“…Representative planar dual-modality images acquired on one of the systems mentioned above obtained from a 250-g rat injected with 99m Tc-MDP are shown in Figure 12, demonstrating radiopharmaceutical uptake in the bone superimposed with an anatomical x-ray image of the rat. 133,142 Gamma Medica 2 Inc. (Northridge, CA) has developed and introduced a small animal SPECT/CT system 137,138 with two compact scintillation cameras 126,143,144 and a high-resolution CT subsystem 138 for dual-modality Figure 11. Top: schematic diagram of the experimental set-up.…”

Section: Small-animal Imaging Systemsmentioning

confidence: 99%