Manipulation of the anabolic and catabolic responses with BMP-2 and zoledronic acid in a rat femoral fracture model

Doi, Yuji; Miyazaki, Masashi; Yoshiiwa, Toyomi; Hara, Katsutoshi; Kataoka, Masashi; Tsumura, Hiroshi

doi:10.1016/j.bone.2011.07.005

Cited by 40 publications

(37 citation statements)

References 27 publications

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“…Although a collagen sponge has been used in previous clinical work as a carrier for rhBMP-2, 4,5 MedGEL releases rhBMP-2 gradually over 4 weeks, allowing for the longer local retention of rhBMP-2 at the implantation site in comparison with a collagen sponge. 24 According to our previous data, 21,22 10 mg of rhBMP-2 was sufficient for bone fusion. A recent study reported that the minimum amount of rhBMP-2 required to achieve a 100% fusion rate in a spinal fusion model was 3.2 mg. 25 1.0 mg of rhBMP-2 was insufficient to achieve 100% bone fusion in this model.…”

Section: Discussionmentioning

confidence: 94%

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Enhancement of the Effects of Exfoliated Carbon Nanofibers by Bone Morphogenetic Protein in a Rat Femoral Fracture Model

Miyazaki

Toyoda

Yoshiiwa

et al. 2014

Journal Orthopaedic Research

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Exfoliated carbon nanofibers (ExCNFs) are expected to serve as excellent scaffolds for promoting and guiding bone-tissue regeneration. We aimed to enhance the effects of ExCNFs with bone morphogenetic proteins (BMPs) and examine their feasibility and safety in clinical applications using a rat femoral fracture model. Group I (n ¼ 16) animals were implanted with control MedGEL. Group II (n ¼ 17) animals were implanted with MedGEL containing ExCNFs. Group III (n ¼ 15) animals were implanted with MedGEL containing 1 mg rhBMP-2. Group IV (n ¼ 15) animals were implanted with MedGEL containing 1 mg rhBMP-2 and ExCNFs. The rats were euthanized after 6 weeks, and their fractured femurs were explanted and assessed by manual palpation, radiographs, and highresolution microcomputerized tomography (micro-CT); the femurs were also subjected to biomechanical and histological analysis. The fusion rates in Group IV (73.3%) were considerably higher than those in Groups I (25. Keywords: exfoliated carbon nanofiber; bone morphogenetic protein; fracture healing; rat femoral fracture model; scaffold Bone morphogenetic proteins (BMPs) are members of the transforming growth factor b superfamily and are powerful osteoinductive molecules. The osteoinductive effects of recombinant human BMPs (rhBMPs) in surgical procedures such as fracture repair, healing of critical-size bone defects, and spinal fusion have been demonstrated in animal models and clinical trials; furthermore, rhBMP-2 and rhBMP-7 have been approved for clinical use. [1][2][3][4][5] Unfortunately, the results of clinical trials show that high doses of BMPs are required to induce adequate bone fusion, as the molecules are soluble and easily diffuse away from the fusion site, becoming inactivated in vivo. 6 In addition, the usefulness of BMPs is limited by their high costs. To address these problems, a number of strategies are being developed to generate safer, less expensive, and more efficacious spinal fusion using rhBMP. However, the efficient immobilization of BMPs onto carriers at low dosage while maintaining desirable in vivo regenerative action remains as a major challenge in bone regeneration research and practice. 7,8 The required rhBMP-2 level in humans, even for the FDA-approved collagen sponge-incorporated treatment, is much higher (over six orders of magnitude greater) than that used for in vitro cell level evaluation and in vivo animal studies. 7,9 Several ongoing investigations aim to develop a scaffold that functions as a delivery vehicle, providing cells with a more controlled and sustained release of bioactive molecules to maintain the local growth factor concentration within the therapeutic range.Carbon nanotubes (CNTs) have received much attention because of their interesting properties, including their exceptional mechanical 10 and high electrical and thermal conductivity, 11 which facilitate their use as reinforcements or additives in materials such as plastics, metals, and ceramics to improve the properties of the materials and introduce nove...

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Section: Discussionmentioning

confidence: 94%

“…20,21 The purpose of the present study was to investigate the enhancement of the effects of ExCNFs by BMP and examine the feasibility and safety of ExCNFs in clinical applications using a rat femoral fracture model.…”

mentioning

confidence: 99%

Enhancement of the Effects of Exfoliated Carbon Nanofibers by Bone Morphogenetic Protein in a Rat Femoral Fracture Model

Miyazaki

Toyoda

Yoshiiwa

et al. 2014

Journal Orthopaedic Research

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“…Clearly, there are benefits to dual combinations over single factors. Other factors and compounds used in combination with rhBMP-2, whether directly or indirectly, included BMP binding protein (BBP) , erythropoietin (Sun et al, 2012a), FGF (Springer et al, 2008), α4-integrin (Kumar et al, 2010a), Runx2 , TGF-β2 (Thorey et al, 2011), tobramycin (Glatt et al, 2009) and zoledronic acid (Doi et al, 2011;Schindeler et al, 2011). A number of studies have incorporated mesenchymal stem cells (MSCs) (Hou et al, 2007;) providing a healthy inducible cell source within the defect site (Dawson et al, 2014).…”

Section: Combination Administration Of Bmp-2mentioning

confidence: 99%

“…It is estimated that 3.6 % of the UK population (of over 64 million) will suffer a bone fracture in their lifetime (Donaldson et al, 2008). The risk of fracture increases with age and statistics show 1 in 3 women and 1 in 5 men over 50 years of age will experience an osteoporotic fracture; a growing concern in an increasingly aged population (van Staa et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Tissue engineered bone using select growth factors: A comprehensive review of animal studies and clinical translation studies in man

Gothard¹,

Smith²,

Kanczler³

et al. 2014

eCM

158

125

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“…BMPs are originally found as a cartilage anabolic factor, which can induce matrix synthesis and promote fracture healing (Doi et al, 2011). Recent studies have shown that BMP6 and BMP7, as the same subgroup of BMPs family, also are responsible for the development of the nervous system and for protection against brain injuries.…”

Section: Introductionmentioning

confidence: 99%

Roles of BMP6/7 in Actin Dynamics in Amyloid β-Induced Neurotoxicity

Sun¹,

Zhang²,

Xiao³

2014

PSYCH

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Actin dynamics plays an important role in many physiological functions such as long-term potentiation, neurotransmission, regulatory proteins translocation, ATP cycle, etc. When amyloid β (Aβ)-induced neurotoxicity occurs, the imbalance of actin dynamics leads to dystrophy of dendrites, which is characteristic pathology in Alzheimer's disease (AD). Transient and persistent Aβ neurotoxicity provokes distinct manifestations of actin dynamics and causes opposing effects in AD. It has been shown that bone morphogenetic protein 6/7 (BMP6/7) protects neuronal morphology against Aβ-induced neurotoxicity, and can directly bind to LIM kinase1 (LIMK1), being one part of the upstream regulatory pathway of actin dynamics. This review aims to discuss a potential mechanism of BMPs underlying maintainance of cytoskeletal stabilization in neurite.

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Manipulation of the anabolic and catabolic responses with BMP-2 and zoledronic acid in a rat femoral fracture model

Cited by 40 publications

References 27 publications

Enhancement of the Effects of Exfoliated Carbon Nanofibers by Bone Morphogenetic Protein in a Rat Femoral Fracture Model

Enhancement of the Effects of Exfoliated Carbon Nanofibers by Bone Morphogenetic Protein in a Rat Femoral Fracture Model

Tissue engineered bone using select growth factors: A comprehensive review of animal studies and clinical translation studies in man

Roles of BMP6/7 in Actin Dynamics in Amyloid β-Induced Neurotoxicity

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