Infusion of islet amyloid polypeptide (150 pmol min-1 kg-1) caused a fall in serum calcium and phosphate concentrations in five patients with Paget's disease of the bone.
Further investigations have proposed that the bony abnormalities seen in Paget's disease are due to the effects of the virus on osteoclastic interleukin-6 and c-FOS production, possibly via the transcription factor NF-kappa B.
Further investigations have proposed that the bony abnormalities seen in Paget's disease are due to the effects of the virus on osteoclastic interleukin-6 and c-FOS production, possibly via the transcription factor NF-kappa B.
Osteoclasts in both osteoarthritic and pagetic bone express IL-6R mRNA and NF-IL-6, but only pagetic osteoclasts expressed IL-6, suggesting that in Paget's diseaseIL-6 can act as an autocrine factor on osteoclasts.
Overexpression of the neu-protein, evidenced as membrane staining by immunohistochemistry, is detected in approximately 20% of invasive duct cell carcinomas, in approximately 50% of in situ duct cell carcinomas, and in almost 100% of cases of Paget's disease.
Overexpression of the neu-protein, evidenced as membrane staining by immunohistochemistry, is detected in approximately 20% of invasive duct cell carcinomas, in approximately 50% of in situ duct cell carcinomas, and in almost 100% of cases of Paget's disease.
Osteoclasts in both osteoarthritic and pagetic bone express IL-6R mRNA and NF-IL-6, but only pagetic osteoclasts expressed IL-6, suggesting that in Paget's disease IL-6 can act as an autocrine factor on osteoclasts.
Overexpression of the neu-protein, evidenced as membrane staining by immunohistochemistry, is detected in approximately 20% of invasive duct cell carcinomas, in approximately 50% of in situ duct cell carcinomas, and in almost 100% of cases of Paget's disease.
In Paget's disease, IL-6 is produced by the osteoclasts, the osteoclasts express IL-6 receptors and IL-6 mRNA, and increased levels of IL-6 are present in the marrow plasma and serum of these patients.
There are abnormalities in the stages of osteoclast development, and studies in Paget's disease have suggested a major role for IL-6 in human osteoclast activity.
In order to investigate the possible role of TNFRSF11A in the pathogenesis of Paget's disease and osteosarcoma, we conducted mutation screening of the TNFRSF11A gene in patients with familial and sporadic Paget's disease as well as DNA extracted from Pagetic bone lesions, an osteosarcoma arising in Pagetic bone and six osteosarcoma cell lines.
These data indicate that TNFRSF11A mutations contribute neither to the vast majority of cases of sporadic or familial PDB, nor to the development of osteosarcoma.
Genetic factors are important in the pathogenesis of PDB, and previous studies have shown that the PDB-like bone dysplasia familial expansile osteolysis is caused by activating mutations in the TNFRSF11A gene that encodes receptor activator of nuclear factor kappa B (RANK); however, linkage studies, coupled with mutation screening, have excluded involvement of RANK in the vast majority of patients with PDB.
We performed mutation analysis in the RANK and OPG genes in 28 PDB patients to investigate whether mutations in these genes could be responsible for PDB.
Hence, autosomal dominant inclusion body myopathy (HIBM), Paget disease of bone (PDB), and frontotemporal dementia (FTD) localizes to a 1.08-6.46 cM critical interval on 9p13.3-12 in the region of autosomal recessive IBM2.