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Intradiscal application of rhBMP-7 does not induce regeneration in a canine model of spontaneous intervertebral disc degeneration

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العنوان: Intradiscal application of rhBMP-7 does not induce regeneration in a canine model of spontaneous intervertebral disc degeneration
المؤلفون: Willems, Nicole, Bach, Frances C, Plomp, Saskia G M, van Rijen, Mattie Hp, Wolfswinkel, Jeannette, Grinwis, Guy Cm, Bos, Clemens, Strijkers, Gustav J, Dhert, Wouter Ja, Meij, Björn P, Creemers, Laura B, Tryfonidou, Marianna A, CSCA TR1, dPB CR, Regenerative Medicine, Stem Cells & Cancer, Orthopedie en neurochirurgie, LS Equine Muscoskeletal Biology, Veterinair Pathologisch Diagnostisch Cnt, Dep Pathobiologie, Pathologie, PB AVM, Faculteit Diergeneeskunde, LS Algemene chirurgie, Sub Neuro/Tandheelkunde
المساهمون: CSCA TR1, dPB CR, Regenerative Medicine, Stem Cells & Cancer, Orthopedie en neurochirurgie, LS Equine Muscoskeletal Biology, Veterinair Pathologisch Diagnostisch Cnt, Dep Pathobiologie, Pathologie, PB AVM, Faculteit Diergeneeskunde, LS Algemene chirurgie, Sub Neuro/Tandheelkunde
المصدر: Arthritis Research & Therapy
Arthritis Research & Therapy, 17. BioMed Central
Arthritis Research & Therapy, 17(1):137, 1-14. BioMed Central
Arthritis Research & Therapy, 17, 1. BioMed Central
سنة النشر: 2014
مصطلحات موضوعية: Male, Pathology, medicine.medical_specialty, Bone Morphogenetic Protein 7, Immunology, Cell, Intervertebral Disc Degeneration, Research Support, Polymerase Chain Reaction, Glycosaminoglycan, Dogs, Rheumatology, Tissue engineering, In vivo, Osteogenesis, medicine, Journal Article, Immunology and Allergy, Animals, Non-U.S. Gov't, business.industry, Regeneration (biology), Research Support, Non-U.S. Gov't, Intervertebral disc, musculoskeletal system, In vitro, Bone morphogenetic protein 7, Disease Models, Animal, medicine.anatomical_structure, business, Research Article
الوصف: Introduction Strategies for biological repair and regeneration of the intervertebral disc (IVD) by cell and tissue engineering are promising, but few have made it into a clinical setting. Recombinant human bone morphogenetic protein 7 (rhBMP-7) has been shown to stimulate matrix production by IVD cells in vitro and in vivo in animal models of induced IVD degeneration. The aim of this study was to determine the most effective dose of an intradiscal injection of rhBMP-7 in a spontaneous canine IVD degeneration model for translation into clinical application for patients with low back pain. Methods Canine nucleus pulposus cells (NPCs) were cultured with rhBMP-7 to assess the anabolic effect of rhBMP-7 in vitro, and samples were evaluated for glycosaminoglycan (GAG) and DNA content, histology, and matrix-related gene expression. Three different dosages of rhBMP-7 (2.5 μg, 25 μg, and 250 μg) were injected in vivo into early degenerated IVDs of canines, which were followed up for six months by magnetic resonance imaging (T2-weighted images, T1rho and T2 maps). Post-mortem, the effects of rhBMP-7 were determined by radiography, computed tomography, and macroscopy, and by histological, biochemical (GAG, DNA, and collagen), and biomolecular analyses of IVD tissue. Results In vitro, rhBMP-7 stimulated matrix production of canine NPCs as GAG deposition was enhanced, DNA content was maintained, and gene expression levels of ACAN and COL2A1 were significantly upregulated. Despite the wide dose range of rhBMP-7 (2.5 to 250 μg) administered in vivo, no regenerative effects were observed at the IVD level. Instead, extensive extradiscal bone formation was noticed after intradiscal injection of 25 μg and 250 μg of rhBMP-7. Conclusions An intradiscal bolus injection of 2.5 μg, 25 μg, and 250 μg rhBMP-7 showed no regenerative effects in a spontaneous canine IVD degeneration model. In contrast, intradiscal injection of 250 μg rhBMP-7, and to a lesser extent 25 μg rhBMP-7, resulted in extensive extradiscal bone formation, indicating that a bolus injection of rhBMP-7 alone cannot be used for treatment of IVD degeneration in human or canine patients. Electronic supplementary material The online version of this article (doi:10.1186/s13075-015-0625-2) contains supplementary material, which is available to authorized users.
وصف الملف: image/pdf; application/pdf
تدمد: 1478-6362
1478-6354
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::91076bdd66b3a82ccf06b3c652eb6913
https://pubmed.ncbi.nlm.nih.gov/26013758
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....91076bdd66b3a82ccf06b3c652eb6913
قاعدة البيانات: OpenAIRE
الوصف
تدمد:14786362
14786354