A murine model of neurofibromatosis type 1 tibial pseudarthrosis featuring proliferative fibrous tissue and osteoclast-like cells

El-Hoss, Jad; Sullivan, Kate; Cheng, Tegan L.; Yu, Na; Bobyn, Justin D.; Peacock, Lauren; Mikulec, Kathy; Baldock, Paul A.; Alexander, Ian E.; Schindeler, Aaron; Little, David

doi:10.1002/jbmr.528

Cited by 42 publications

(61 citation statements)

References 30 publications

(37 reference statements)

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“…Mice underwent a closed fracture (i.e., the periosteum remained intact) with injection of AdCre into the fracture site for transduction of local cells. As previously established 18 …”

Section: In Vivo Fluorescence Cell Trackingmentioning

confidence: 99%

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A Combination of rhBMP-2 (Recombinant Human Bone Morphogenetic Protein-2) and MEK (MAP Kinase/ERK Kinase) Inhibitor PD0325901 Increases Bone Formation in a Murine Model of Neurofibromatosis Type I Pseudarthrosis

El-Hoss

Cheng

Carpenter

et al. 2014

The Journal of Bone and Joint Surgery

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“…Mice underwent a closed fracture (i.e., the periosteum remained intact) with injection of AdCre into the fracture site for transduction of local cells. As previously established 18 …”

Section: In Vivo Fluorescence Cell Trackingmentioning

confidence: 99%

“…In 2012, we described a new surgical model of NF1 pseudarthrosis that features localized double inactivation of the Nf1 gene in a fracture 18 . In this model, Nf1 flox/flox mice are injected with a Cre-expressing adenovirus (AdCre) at the site of a tibial fracture, causing the local deletion of both Nf1 genes and resulting in a fibrous pseudarthrosis.…”

mentioning

confidence: 99%

A Combination of rhBMP-2 (Recombinant Human Bone Morphogenetic Protein-2) and MEK (MAP Kinase/ERK Kinase) Inhibitor PD0325901 Increases Bone Formation in a Murine Model of Neurofibromatosis Type I Pseudarthrosis

El-Hoss

Cheng

Carpenter

et al. 2014

The Journal of Bone and Joint Surgery

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“…We propose that the formation of periosteal hamartoma in congenital pseudarthrosis is due to abnormally high proliferation associated with poor differentiation capability of mesenchymal stem cells (El-Hoss et al, 2012) residing in the local periosteum due to non-functional negative regulation of Ras signalling pathway in neurofibromatosis (Abramowicz and Gos, 2013). Bisphosphonates should support the differentiation by regulating the Ras protein in BM MSCs (von Knoch et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Does pamidronate enhance the osteogenesis in mesenchymal stem cells derived from fibrous hamartoma in congenital pseudarthrosis of the tibia?

et al. 2016

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Neurofibromatosis type 1 (NF1) is a commonly occurring genetic disorder in children. Mutation in the NF1 gene has its implication in poor osteoblastic capabilities. We hypothesised that pamidronate will enhance the osteoblastic potential of the mesenchymal stem cells (MSCs) derived from lipofibromatosis tissue of children with congenital pseudarthrosis tibia (CPT) associated with NF1. In this study, bone marrow MSCs (BM MSCs) and CPT MSCs were obtained from three patients undergoing salvage surgeries/bone grafting (healthy controls) and those undergoing excision of the hamartoma and corrective surgeries respectively. The effects of pamidronate (0, 10 nM, 100 nM and 1 μM) on cell proliferation, toxicity and differentiation potential were assessed and the outcome was measured by staining and gene expression. Our outcome showed that CPT MSCs had more proliferation rate as compared to BM MSCs. All 3 doses of pamidronate did not cause any toxicity to the cells in both the groups. The CPT MSCs showed less differentiation with pamidronate compared to the healthy control MSCs. This was quantitated by staining and gene expression analysis. Therefore, supplementation with pamidronate alone will not aid in bone formation in patients diagnosed with CPT. An additional stimulus is required to enhance bone formation.

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“…The aetiology is unclear but there is a strong association between CPT and neurofibromatosis type I (NF-I). Histological examination has shown hyperplasia of fibroblasts within the periosteum [3][4][5] and a better understanding of the role of NF-1 has suggested that the defect results from failure of osteoblastic differentiation [6,7]. CPT is challenging to treat and, historically, amputation rates of up to 50 % have been reported [8,9].…”

Section: Introductionmentioning

confidence: 99%

Congenital pseudarthrosis of the tibia: The results of an evolving protocol of management

Nicolaou

Ghassemi

Hill

2013

Journal of Children's Orthopaedics

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Purpose This retrospective cohort study assesses the outcomes of a protocol of management, based on the recommendations of the European Paediatric Orthopaedic Society (EPOS) multi-centre study, for the management of congenital pseudarthrosis of the tibia. Methods Utilising an incremental protocol of bracing, intramedullary rods and circular frame fixation with or without bone morphogenetic protein-2 (BMP-2), 11 patients had reached skeletal maturity or had follow up of 5 years from radiological union of the pseudarthrosis. Demographic data, deformity parameters before and after treatment, and functional outcome scores were recorded. Results Ten of the 11 patients successfully healed and two sustained a refracture. All deformity parameters improved and a mean leg length discrepancy of 2.5 cm (range 0–7.5 cm) existed at the time of the last follow up. Some pseudarthroses healed with deformity correction and rod insertion alone. Six of the 11 patients had a confirmed diagnosis of neurofibromatosis and nine had sustained a fracture before 4 years of age. Refracture was associated with malalignment after healing. Conclusion This method of treatment provides a successful stepwise protocol for the management of this complex disorder, avoiding the use of aggressive limb reconstruction techniques at a young age in some cases. Level of evidenceCase series Level IV.

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A murine model of neurofibromatosis type 1 tibial pseudarthrosis featuring proliferative fibrous tissue and osteoclast-like cells

Cited by 42 publications

References 30 publications

A Combination of rhBMP-2 (Recombinant Human Bone Morphogenetic Protein-2) and MEK (MAP Kinase/ERK Kinase) Inhibitor PD0325901 Increases Bone Formation in a Murine Model of Neurofibromatosis Type I Pseudarthrosis

A Combination of rhBMP-2 (Recombinant Human Bone Morphogenetic Protein-2) and MEK (MAP Kinase/ERK Kinase) Inhibitor PD0325901 Increases Bone Formation in a Murine Model of Neurofibromatosis Type I Pseudarthrosis

Does pamidronate enhance the osteogenesis in mesenchymal stem cells derived from fibrous hamartoma in congenital pseudarthrosis of the tibia?

Congenital pseudarthrosis of the tibia: The results of an evolving protocol of management

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