Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0005940 (bone disease)
 7,459 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies of osteoclasts and their precursors in normal and pathological states have been severely hampered by the lack of an in vitro system for forming osteoclasts. We developed a human marrow culture system in which multinucleated cells with several characteristics of osteoclasts form. Multinucleated cells began to form during the first week of culture, with maximum numbers formed after 3 weeks. PTH (25-50 ng/ml) and 1,25-dihydroxyvitamin D3 (10(-10)-10(-8) M) increased formation of these cells, and these effects were inhibited by calcitonin. These multinucleated cells contained nonspecific esterase and tartrate-resistant acid phosphatase, a marker enzyme of osteoclasts, and had several ultrastructural features of osteoclasts. We used this marrow cell culture technique to study a patient with hyperparathyroidism and markedly increased osteoclasts on bone marrow biopsy. The marrow from this patient formed increased numbers of multinucleated cells in vitro. After parathyroidectomy both multinucleated cell formation in vitro and osteoclast numbers on bone biopsy decreased significantly. This long term marrow culture system represents the first demonstration of human osteoclast-like cell formation in vitro. This system should permit studies to evaluate factors controlling formation of cells with certain osteoclast characteristics in vitro and their precursors as well as to evaluate abnormalities in osteoclast formation in patients with metabolic bone disease.
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PMID:Formation of multinucleated cells that respond to osteotropic hormones in long term human bone marrow cultures. 356 33

Autosomal dominant osteopetrosis type II (ADO II) is a rare, heritable bone disorder characterized by a high bone mass and insufficient osteoclast activity. Mutations in the CLCN7 gene have been reported to cause ADO II. To gain novel insights into the pathways dysregulated in ADOII osteoclasts, we identified changes in gene expression in osteoclasts from patients with a heterozygous mutation of CLCN7. To do this, we carried out a transcriptomic study comparing gene expression in the osteoclasts of patients with ADO II and healthy donors. Our data show that, according to our selection criteria, 182 genes were differentially expressed in osteoclasts from patients and controls. From the 18 displaying the highest change in microarray, we confirmed differential expression for seven by qPCR. Although two of them have previously been found to be expressed in osteoclasts (ITGB5 and SERPINE2), the other five (CES1 (carboxyl esterase 1), UCHL1 (ubiquitin carboxy-terminal esterase L1, also known as ubiquitin thiolesterase), WARS (tryptophanyl-tRNA synthetase), GBP4 (guanylate-binding protein 4), and PRF1) are not yet known to have a role in this cell type. At the protein level, we confirmed elevated expression of ITGB5 and reduced expression of WARS, PRF1, and SERPINE2. Transfection of ClC-7 harboring the G215R mutation into osteoclasts resulted in an increased ITGB5 and reduced PRF1 expression of borderline significance. Finally, we observed that the ADO II patients presented a normal or increased serum level of bone formation markers, demonstrating a coupling between dysfunctional osteoclasts and osteoblasts. Sphingosine kinase 1 mRNA was expressed at the same level in ADO II and control osteoclasts. In conclusion, these data suggest that in addition to an acidification dysfunction caused by the CLCN7 mutation, a change in ITGB5, PRF1, WARS, and SERPINE2 expression could be part of the osteoclastic phenotype of ADO II.
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PMID:Differentially expressed genes in autosomal dominant osteopetrosis type II osteoclasts reveal known and novel pathways for osteoclast biology. 2433 69