Deficiency of inducible and endothelial nitric oxide synthase results in diminished bone formation and delayed union and nonunion development
| Autor: | Dennis M. Meesters, Martijn Poeze, S Neubert, Prg Brink, K. A. P. Wijnands, Keita Ito, Frans Heyer, Stephan Zeiter |
|---|---|
| Přispěvatelé: | Orthopaedic Biomechanics, Promovendi NTM, RS: NUTRIM - R2 - Gut-liver homeostasis, Surgery, RS: NUTRIM - R3 - Chronic inflammatory disease and wasting, MUMC+: TPZ Netwerk Acute Zorg Limburg (9), MUMC+: MA Heelkunde (9) |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Physiology Endocrinology Diabetes and Metabolism Nitric Oxide Synthase Type II Fracture healing chemistry.chemical_compound 0302 clinical medicine Osteogenesis Amino Acids Bony Callus 030222 orthopedics L-ARGININE biology Nitric Oxide Synthase Type III LOCALIZATION Up-Regulation Nonunion Myeloperoxidase Female EXPRESSION medicine.medical_specialty Histology Delayed union ISOFORMS Bone healing Arginine Nitric oxide FRACTURE REPAIR 03 medical and health sciences Internal medicine medicine Animals Femur RNA Messenger Peroxidase Osteosynthesis Arginase Wild type X-Ray Microtomography medicine.disease Surgery Mice Inbred C57BL MICE 030104 developmental biology Endocrinology chemistry Fractures Ununited biology.protein |
| Zdroj: | Bone, 83, 111-118. Elsevier Bone, 83, 111-118. Elsevier Science |
| ISSN: | 1873-2763 8756-3282 |
| DOI: | 10.1016/j.bone.2015.11.006 |
| Popis: | Background Between 5% and 10% of all fractures fail to heal adequately resulting in nonunion of the fracture fragments. This can significantly decrease a patient's quality of life and create associated psychosocial and socio-economic problems. Nitric oxide (NO) and nitric oxide synthases (NOS) have been found to be involved in fracture healing, but until now it is not known if disturbances in these mechanisms play a role in nonunion and delayed union development. In this study, we explored the role of endothelial and inducible NOS deficiency in a delayed union model in mice. Materials and methods A 0.45 mm femur osteotomy with periosteal cauterization followed by plate-screw osteosynthesis was performed in the left leg of 20–24 week old wild type, Nos2 −/− and Nos3 −/− mice. Contralateral unfractured legs were used as a control. Callus volume was measured using micro-computed tomography (μCT) after 28 and 42 days of fracture healing. Immuno histochemical myeloperoxidase (MPO) staining was performed on paraffin embedded sections to assess neutrophil influx in callus tissue and surrounding proximal and distal marrow cavities of the femur. After 7 and 28 days of fracture healing, femurs were collected for amino acid and RNA analysis to study arginine-NO metabolism. Results With μCT, delayed union was observed in wild type animals, whereas in both Nos2 −/− and Nos3 −/− mice nonunion development was evident. Both knock-out strains also showed a significantly increased influx of MPO when compared with wild type mice. Concentrations of amino acids and expression of enzymes related to the arginine-NO metabolism were aberrant in NOS deficient mice when compared to contralateral control femurs and wild type samples. Discussion and conclusion In the present study we show for the first time that the absence of nitric oxide synthases results in a disturbed arginine-NO metabolism and inadequate fracture healing with the transition of delayed union into a nonunion in mice after a femur osteotomy. Based on these data we suggest that the arginine-NO metabolism may play a role in the prevention of delayed unions and nonunions. |
| Databáze: | OpenAIRE |
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