Macrophage colony-stimulating factor and receptor activator NF-κB ligand fail to rescue osteoclast-poor human malignant infantile osteopetrosis in vitro

Flanagan, Adrienne M.; Massey, Helen M.; Wilson, Callum; Vellodi, Ashok; Horton, Michael A.; Steward, Colin G.

doi:10.1016/s8756-3282(01)00656-1

Cited by 23 publications

(12 citation statements)

References 30 publications

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“…In all studies, osteoclasts formed, but were defective in bone resorption. Osteoclast formation was impaired in cultures with blood cells from a patient with an "osteoclast poor" form of the disease (Flanagan et al, 2002). So, in all studies reported thus far, osteoclasts appeared functionally similar in vivo and in vitro.…”

Section: Studies Of Osteopetrotic Osteoclasts In Vitromentioning

confidence: 88%

“…3A), illustrating that osteoclast function, not differentiation, is affected Shapiro et al, 1988). However, in a small number of cases osteoclasts are absent in bone biopsies, which demonstrates that further heterogeneity exists and that impairment of osteoclast formation does occur in a subset of cases (Flanagan et al, 2002). Information on osteoclast phenotype and ultrastructure is rather scant and most reports in the literature concentrate on severe cases of malignant osteopetrosis.…”

Section: Bone Histology and Osteoclast Phenotypementioning

confidence: 99%

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Osteoclast diseases

Helfrich

2003

Microscopy Res & Technique

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Osteoclasts are the only cells capable of resorbing mineralised bone, dentine and cartilage. Osteoclasts act in close concert with bone forming osteoblasts to model the skeleton during embryogenesis and to remodel it during later life. A number of inherited human conditions are known that are primarily caused by a defect in osteoclasts. Most of these are rare monogenic disorders, but others, such as the more common Paget's disease, are complex diseases, where genetic and environmental factors combine to result in the abnormal osteoclast phenotype. Where the genetic defect gives rise to ineffective osteoclasts, such as in osteopetrosis and pycnodysostosis, the result is the presence of too much bone. However, the phenotype in many osteoclast diseases is a combination of osteosclerosis with osteolytic lesions. In such conditions, the primary defect is hyperactivity of osteoclasts, compensated by a secondary increase in osteoblast activity. Rapid progress has been made in recent years in the identification of the causative genes and in the understanding of the biological role of the proteins encoded. This review discusses the known osteoclast diseases with particular emphasis on the genetic causes and the resulting osteoclast phenotype. These human diseases highlight the critical importance of specific proteins or signalling pathways in osteoclasts.

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Section: Studies Of Osteopetrotic Osteoclasts In Vitromentioning

confidence: 88%

Section: Bone Histology and Osteoclast Phenotypementioning

confidence: 99%

Osteoclast diseases

Helfrich

2003

Microscopy Res & Technique

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“…Human osteopetroses in most, but not all, cases (12) show normal or increased numbers of osteoclasts, and it has been suggested that in humans, the affected gene(s) is more likely to relate to the maintenance of the functional capacity of mature osteoclasts. This suggestion has been supported by the fact that the gene defects found thus far in ARO and ADO‐II, as well as the one found in osteopetrosis associated to renal tubular acidosis (OMIM 259730), are all involved in the metabolic pathways leading to acidification of the external microenvironment.…”

Section: Introductionmentioning

confidence: 99%

Chloride Channel ClCN7 Mutations Are Responsible for Severe Recessive, Dominant, and Intermediate Osteopetrosis

Frattini

Pangrazio

Susani

et al. 2003

Journal of Bone and Mineral Research

208

159

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Among 94 osteopetrotic patients presenting with a severe clinical picture and diagnosed early in life, 12 bore mutations in the ClCN7 gene, but only 7 of them had the expected two recessive mutations. The remaining five patients seem to be heterozygous for a ClCN7 mutation, and significant variations were observed in the clinical manifestations of their disease, even within the same family.Introduction: Human osteopetroses are a heterogeneous group of diseases that include both infantile severe, autosomal recessive (ARO) and adult autosomal dominant (ADO) forms. Two genes, Atp6a3 (TCIRG1) and ClCN7, have been shown to be associated with human ARO, the latter of which is also thought to be responsible for ADO-II. However, patients with an intermediate phenotype have been described: the genetic basis of these observances is unknown. Materials and Methods:In this study, we report the clinical and molecular analysis of 94 patients in which a diagnosis of severe osteopetrosis was made within the first 2 years of age. Both TCIRG1 and CLCN7 genes were sequenced in all patients and the molecular findings were correlated to clinical parameters. Results and Conclusions:In 56 of 94 patients with a classical picture of ARO, TCIRG1-dependent recessive mutations were found. In contrast, ClCN7 mutations were found in 12 cases (13%) of severe osteopetrosis, but only 7 of them had two recessive mutations identified: in 6 of these 7 cases, central nervous system manifestations were noted, and these patients had a poor prognosis. The remaining five cases were heterozygous for a ClCN7 mutation,

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“…A fluorescence microscope was utilized to detect and visualize the distribution of actin rings. Osteoclasts displayed full actin rings or disrupted actin rings with more than 50% intact 17,18. M and MM group cells revealed well-formed actin rings compared to the NC group cells which showed no actin rings.…”

Section: Discussionmentioning

confidence: 85%

Magnesium vs. machined surfaced titanium - osteoblast and osteoclast differentiation

2014

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PURPOSEThis study focused on in vitro cell differentiation and surface characteristics in a magnesium coated titanium surface implanted on using a plasma ion source.MATERIALS AND METHODS40 commercially made pure titanium discs were prepared to produce Ti oxide machined surface (M) and Mg-incorporated Ti oxide machined surface (MM). Surface properties were analyzed using a scanning electron microscopy (SEM). On each surface, alkaline phosphatase (ALP) activity, alizarin red S staining for mineralization of MC3T3-E1 cells, and quantitative analysis of osteoblastic gene expression, were evaluated. Actin ring formation assay and gene expression analysis of TRAP and GAPDH performing RT-PCR were performed to characterize osteoclast differentiation on mouse bone marrow-derived macrophages (BMMs).RESULTSMM showed similar surface morphology and surface roughness with M, but was slightly smoother after ion implantation at the micron scale. M was more hydrophobic than MM. No significant difference between surfaces on ALP activity at 7 and 14 days were observed. Real-time PCR analyses showed similar levels of mRNA expression of the osteoblast phenotype genes; osteopontin (OPN), osteocalcin (OCN), bone sialoprotein (BSP), and collagen 1 (Col 1) in cell grown on MM at 7, 14 and 21 days. Alizarin red S staining at 21 days showed no significant difference. BMMs differentiation increased in M and MM. Actin ring formation assay and gene expression analysis of TRAP showed osteoclast differentiation to be more active on MM.CONCLUSIONBoth M and MM have a good effect on osteoblastic cell differentiation, but MM may speed the bone remodeling process by activating on osteoclast differentiation.

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Macrophage colony-stimulating factor and receptor activator NF-κB ligand fail to rescue osteoclast-poor human malignant infantile osteopetrosis in vitro

Cited by 23 publications

References 30 publications

Osteoclast diseases

Osteoclast diseases

Chloride Channel ClCN7 Mutations Are Responsible for Severe Recessive, Dominant, and Intermediate Osteopetrosis

Magnesium vs. machined surfaced titanium - osteoblast and osteoclast differentiation

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