Osteoclasts in neurofibromatosis type 1 display enhanced resorption capacity, aberrant morphology, and resistance to serum deprivation
| Autor: | Sirkku Peltonen, Maria H. Alanne, Eetu Heervä, Teuvo Hentunen, Juha Peltonen, Tommi Kuorilehto, Kalervo Väänänen |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Serum congenital hereditary and neonatal diseases and abnormalities Pathology medicine.medical_specialty Neurofibromatosis 1 Histology Adolescent Physiology Endocrinology Diabetes and Metabolism Osteoporosis Osteoclasts Culture Media Serum-Free Bone resorption Bone remodeling Young Adult Osteoclast medicine Animals Humans Bone Resorption Progenitor cell Neurofibromatosis Cell Shape neoplasms Cells Cultured business.industry Macrophage Colony-Stimulating Factor Stem Cells RANK Ligand Middle Aged medicine.disease eye diseases nervous system diseases Resorption Osteopenia medicine.anatomical_structure Cattle Female business |
| Zdroj: | Bone. 47:583-590 |
| ISSN: | 8756-3282 |
| Popis: | Neurofibromatosis 1 syndrome (NF1) presents with skeletal involvement suggesting that altered bone dynamics is associated with NF1. Histological analysis of three cases of NF1-related pseudarthrosis revealed numerous osteoclasts in contact with adjacent bone, and within the pseudarthrosis tissue itself. These findings prompted us to evaluate the differentiation and resorption capacity of NF1-osteoclast like cells (OLCs) in vitro. Osteoclast progenitors were isolated from peripheral blood of 17 patients with NF1 and allowed to differentiate into OLCs on bone slices. The following differences were found between NF1 and control samples: samples from NF1 patients resulted in a higher number of resorbing OLCs; NF1 OLCs were larger in size; their nuclei were more numerous; actin rings were more frequent; and the resorption pits in NF1 samples were more numerous and larger. Bone resorption markers revealed that the resorption activity in NF1 OLC cultures was approximately two times higher than in controls. Following deprivation from serum, the number of NF1 OLCs remained essentially the same during 24h, whereas the number of control OLCs was dramatically reduced during the same time. Three patients had NF1-related lytic bone lesions, and their in vitro results differed from those of other patients. Our results demonstrate that OLCs derived from blood of patients with NF1 display elevated resorption activity under conditions isolated from microenvironment operative in vivo. Thus, increased osteoclast activity may be a phenotypic property of the NF1 syndrome, and at least in part explain selected skeletal findings in NF1, such as osteoporosis/osteopenia. |
| Databáze: | OpenAIRE |
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