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)

Major contributions to and confirmations of osteoclast biology have been made by experimental investigations of the osteopetrotic mutations in mammals. Congenital osteopetrosis is a bone disease characterized by a generalized increase in skeletal mass due to decreased osteoclast function. Abnormalities of skeletal growth and the failures of marrow cavity development and tooth eruption are secondary to reduced bone resorption of heterogeneous cause. Elucidation of pathogenetic pathways and unraveling of the cell biology of the osteoclast have proceeded hand-in-hand. This is illustrated by the variable differentiation and activation of osteoclasts among mutations and by demonstrations that the disease in certain animals and children can be cured by providing competent stem cells for osteoclasts via bone marrow transplantation. Congenital absence of carbonic anhydrase II (CA II) in children results in a syndrome that included osteopetrosis because osteoclasts are unable to function in the absence of CA II. The resistance of all mutations to the hypercalcemic effects of parathyroid hormone and recent reports of elevated blood levels of 1,25 dihydroxyvitamin D have broadened the scope of pathogenetic possibilities for osteopetrosis and regulatory possibilities for osteoclasts. Immunological effects including reductions in natural killer cell activity, superoxide and interleukin-2 production make osteopetrotic mutants potential models for studying the role of the immune system in osteoclast biology. Furthermore, coexistence of osteopetrosis with rickets and osteoblast abnormalities and the failure of cell transplants to cure the disease in some mutations illustrate the utility of the osteopetroses for exploring the role of matrix as mentor in osteoclast biology. Thus, understanding congenital osteopetrosis and osteoclast biology are likely to continue together.
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PMID:Osteoclast biology: lessons from mammalian mutations. 268 80

Creatine kinase (CK) isoenzyme BB-CK is predominantly found in brain and is not normally detected in the blood. A few recent reports, however, have described BB-CK in serum from several patients with osteopetrosis (OP). To evaluate the presence and specificity of BB-CK in serum in the osteopetroses among disorders that increase skeletal mass, we quantitated total CK activity and CK isoenzymes in 15 patients representing the five major clinical forms of OP (2 infantile, 3 intermediate, 7 adult [2 type I, 5 type II], and 3 carbonic anhydrase II [CA II] deficiency cases) and in 22 patients representing 14 other types of sclerosing bone disease. All OP patients (except the two adult type I subjects) had BB-CK readily detected in their serum. Conversely, only 1 of the 22 patients with other sclerosing bone disorders had detectable BB-CK in serum (1 of 3 patients with fibrodysplasia [myositis] ossificans progressiva who had barely measurable activity). In three OP patients (one of two with the infantile form and two of five with adult, type II disease), BB-CK values were sufficiently high that serum total CK activity was elevated. In a newborn with malignant OP, both cord blood plasma and peripheral blood serum had substantial amounts of BB-CK. In three subjects (with adult type II OP), who were restudied 2-6 years later, BB-CK was still elevated in their blood. BB-CK in serum appears to distinguish the osteopetroses among the sclerosing bone disorders. Absence of serum BB-CK in adult type I disease suggests that this condition may not be a genuine form of OP. Assay of BB-CK in fetal blood could be studied as a means for prenatal diagnosis of malignant OP. Why the osteoclast failure that characterizes all true forms of OP is associated with BB-CK in the circulation is a new question for skeletal biologists.
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PMID:Creatine kinase brain isoenzyme (BB-CK) presence in serum distinguishes osteopetroses among the sclerosing bone disorders. 888 43

Osteopetrosis in laboratory animals is a metabolic bone disease characterized by increased skeletal mass. It is inherited as an autosomal recessive and results from a defect in the development and/or function of osteoclasts. We studied two enzymes essential for bone resorption, carbonic anhydrase II isoenzyme (CA II) and H+ -ATPase, in osteoclasts from four osteopetrotic mutations in the rat; namely incisors-absent (ia), osteopetrosis (op), toothless (tl), and microphthalmia (mib), to test the hypothesis that reduced bone resorption in one or more of these mutations results from defects in the synthesis or activity of one of these enzymes. CA II was present in most osteoclasts from normal, tl, op, and mib littermates and was homogeneously distributed in cytoplasm. CA II staining in ia osteoclasts was more variable and less intense than in the other mutations. H+-ATPase was also present in osteoclasts from normal animals and mutants and immunostaining showed clear polarization to the ruffled border region in all normal rats and mutants except ia, which showed diffuse distribution of staining in the cytoplasm. H+-ATPase activity (proton transport) in a related tissue, kidney, was normal in tl and ia rats but increased in op and mib rats compared to their normal littermates. These results suggest that the osteoclasts in osteopetrotic rat mutations are not abnormal with respect to the distribution of CA II and H+ -ATPase and that the function of these enzymes in the skeleton, while likely normal, needs to be tested directly in bone.
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PMID:Carbonic anhydrase II and H+ -ATPase in osteoclasts of four osteopetrotic mutations in the rat. 993 Aug 84