Erratum to: Could an osteoinductor result in degeneration of a neurofibroma in NF1?

Steib, Jean-Paul; Bouchaïb, Julia; Walter, Axel; Schuller, S.; Charles, Yann Philippe

doi:10.1007/s00586-010-1470-2

Cited by 7 publications

(8 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…20 However, a recent case report has highlighted a potential risk of increased transformation of tissue into a neurofibroscarcoma with rhBMP treatment, and this will need to be monitored as the use of BMPs increases. 29 Another concern is that BMPs are reported to stimulate osteoclastic resorption 24,30 and NF1-deficient osteoclast progenitors are particularly sensitised to pro-osteoclastic Histological assessment of the fracture was performed for wild type (a and c) and NF1-deficient mice (b and d), treated with bone morphogenetic protein (BMP-2) alone (a and b) or with BMP-2 and zoledronic acid (c and d) (picrosirius Red/Alcian Blue, × 200 magnification; Aperio Scanscope Software). Increased callus can be seen in samples treated with zoledronic acid.…”

Section: Discussionmentioning

confidence: 97%

Distal tibial fracture repair in a neurofibromatosis type 1-deficient mouse treated with recombinant bone morphogenetic protein and a bisphosphonate

Birke

Morse

et al. 2011

The Journal of Bone and Joint Surgery. British volume

View full text Add to dashboard Cite

Congenital pseudarthrosis of the tibia is an uncommon manifestation of neurofibromatosis type 1 (NF1), but one that remains difficult to treat due to anabolic deficiency and catabolic excess. Bone grafting and more recently recombinant human bone morphogenetic proteins (rhBMPs) have been identified as pro-anabolic stimuli with the potential to improve the outcome after surgery. As an additional pharmaceutical intervention, we describe the combined use of rhBMP-2 and the bisphosphonate zoledronic acid in a mouse model of NF1-deficient fracture repair. Fractures were generated in the distal tibiae of neurofibromatosis type 1-deficient (Nf1(+/-)) mice and control mice. Fractures were open and featured periosteal stripping. All mice received 10 μg rhBMP-2 delivered in a carboxymethylcellulose carrier around the fracture as an anabolic stimulus. Bisphosphonate-treated mice also received five doses of 0.02 mg/kg zoledronic acid given by intraperitoneal injection. When only rhBMP but no zoledronic acid was used to promote repair, 75% of fractures in Nf1(+/-) mice remained ununited at three weeks compared with 7% of controls (p < 0.001). Systemic post-operative administration of zoledronic acid halved the rate of ununited fractures to 37.5% (p < 0.07). These data support the concept that preventing bone loss in combination with anabolic stimulation may improve the outcome following surgical treatment for children with congenital pseudarthosis of the tibia and NF1.

show abstract

Section: Discussionmentioning

confidence: 97%

Distal tibial fracture repair in a neurofibromatosis type 1-deficient mouse treated with recombinant bone morphogenetic protein and a bisphosphonate

Birke

Morse

et al. 2011

The Journal of Bone and Joint Surgery. British volume

View full text Add to dashboard Cite

show abstract

“…34 Studies have reported its risks to premature suture fusion in the growing skeleton, osteolysis, malignant degeneration, and ectopic bone formation, calling into question the safety of recombinant human bone morphogenetic protein-2 in the growing craniofacial skeleton. 4,[35][36][37] These adverse sequelae have driven the investigation of alternative pediatric osteogenic agents, such as the recently described adenosine receptor pathway.…”

Section: Discussionmentioning

confidence: 99%

Bone Tissue Engineering in the Growing Calvaria Using Dipyridamole-Coated, Three-Dimensionally–Printed Bioceramic Scaffolds: Construct Optimization and Effects on Cranial Suture Patency

Maliha

Lopez

Coelho

et al. 2020

Plastic &Amp; Reconstructive Surgery

View full text Add to dashboard Cite

Background: Three-dimensionally-printed bioceramic scaffolds composed of β-tricalcium phosphate delivering the osteogenic agent dipyridamole can heal critically sized calvarial defects in skeletally mature translational models. However, this construct has yet to be applied to growing craniofacial models. In this study, the authors implanted three-dimensionally-printed bioceramic/ dipyridamole scaffolds in a growing calvaria animal model and evaluated bone growth as a function of geometric scaffold design and dipyridamole concentration. Potential adverse effects on the growing suture were also evaluated.Methods: Bilateral calvarial defects (10 mm) were created in 5-week-old (approximately 1.1 kg) New Zealand White rabbits (n = 16 analyzed). Three-dimensionally-printed bioceramic scaffolds were constructed in quadrant form composed of varying pore dimensions (220, 330, and 500 μm). Each scaffold was coated with collagen and soaked in varying concentrations of dipyridamole (100, 1000, and 10,000 μM). Controls consisted of empty defects. Animals were killed 8 weeks postoperatively. Calvariae were analyzed using micro-computed tomography, three-dimensional reconstruction, and nondecalcified histologic sectioning.Results: Scaffold-induced bone growth was statistically greater than bone growth in empty defects (p = 0.02). Large scaffold pores, 500 μm, coated in 1000 μM dipyridamole yielded the most bone growth and lowest degree of scaffold presence within the defect. Histology showed vascularized woven and lamellar bone along with initial formation of vascular canals within the scaffold lattice. Micro-computed tomographic and histologic analysis revealed patent calvarial sutures without evidence of ectopic bone formation across all dipyridamole concentrations.

show abstract

“…From the DS-10, Bmp2 was chosen for further study based on (i) the significance in GSEA, and (ii) the positive association between Bmp2 expression and increasing malignancy of NF1-related tissues in the data of Miller and colleagues (13). In addition, a case report suggested a connection between acute deterioration of plexiform neurofibroma to MPNST and BMP2 treatment intended to facilitate bone fusion after surgery (41). Bmp2 overexpression resulting from Nf1 deficiency but independent of NRAS and MEK1/2 activities was verified in MPNST cells by qPCR.…”

Section: Discussionmentioning

confidence: 99%

RAS/MEK–Independent Gene Expression Reveals BMP2-Related Malignant Phenotypes in the Nf1-Deficient MPNST

Sun

Haddad

Kraniak

et al. 2013

Molecular Cancer Research

View full text Add to dashboard Cite

Malignant peripheral nerve sheath tumor (MPNST) is a type of soft tissue sarcoma that occurs in carriers of germline mutations in Nf1 gene as well as sporadically. Neurofibromin, encoded by the Nf1 gene, functions as a GTPase-activating protein (GAP) whose mutation leads to activation of wt-RAS and mitogen-activated protein kinase (MAPK) signaling in neurofibromatosis type I (NF1) patients' tumors. However, therapeutic targeting of RAS and MAPK have had limited success in this disease. In this study, we modulated NRAS, mitogen-activated protein/extracellular signal-regulated kinase (MEK)1/2, and neurofibromin levels in MPNST cells and determined gene expression changes to evaluate the regulation of signaling pathways in MPNST cells. Gene expression changes due to neurofibromin modulation but independent of NRAS and MEK1/2 regulation in MPNST cells indicated bone morphogenetic protein 2 (Bmp2) signaling as a key pathway. The BMP2-SMAD1/5/8 pathway was activated in NF1-associated MPNST cells and inhibition of BMP2 signaling by LDN-193189 or short hairpin RNA (shRNA) to BMP2 decreased the motility and invasion of NF1-associated MPNST cells. The pathway-specific gene changes provide a greater understanding of the complex role of neurofibromin in MPNST pathology and novel targets for drug discovery. Mol Cancer Res; 11(6); 616-27. Ó2013 AACR.

show abstract

Erratum to: Could an osteoinductor result in degeneration of a neurofibroma in NF1?

Cited by 7 publications

References 0 publications

Distal tibial fracture repair in a neurofibromatosis type 1-deficient mouse treated with recombinant bone morphogenetic protein and a bisphosphonate

Distal tibial fracture repair in a neurofibromatosis type 1-deficient mouse treated with recombinant bone morphogenetic protein and a bisphosphonate

Bone Tissue Engineering in the Growing Calvaria Using Dipyridamole-Coated, Three-Dimensionally–Printed Bioceramic Scaffolds: Construct Optimization and Effects on Cranial Suture Patency

RAS/MEK–Independent Gene Expression Reveals BMP2-Related Malignant Phenotypes in the Nf1-Deficient MPNST

Contact Info

Product

Resources

About