title: Bone marrow-derived osteoclast-like cells from a patient with craniometaphyseal dysplasia lack expression of osteoclast-reactive vacuolar proton pump.
abstract: Craniometaphyseal dysplasia (CMD) is a rare craniotubular bone dysplasia transmitted in autosomal dominant or recessive form. This disease is characterized by cranial bone hyperostosis and deformity of the metaphyses of the long bones. Using osteoclast-like cells formed from patient bone marrow cells, we investigated the pathophysiology of CMD in a 3-yr-old patient. Untreated bone marrow cells from the patient differentiated into osteoclast-like cells in vitro. These cells were shown to have vitronectin beta-receptors using a specific monoclonal antibody, i.e., 23C6 (CD51), which reacts with osteoclasts in human bone biopsy samples. However, the number of these osteoclast-like cells formed from the patient's bone marrow was only 40% of the normal controls. 1,25-dihydroxyvitamin-D3, bovine 1-34 parathyroid hormone, recombinant human interleukin-1 beta, recombinant human interleukin-6, or recombinant human macrophage colony-stimulating factor significantly increased, while salmon calcitonin significantly inhibited, the number of osteoclast-like cells. However, these cells could not resorb sperm whale dentin slices and lacked the osteoclast-reactive vacuolar proton pump as evidenced by a monoclonal antibody (E11). Western blot analysis using a monoclonal antibody to pp60c-src (327) revealed that protooncogene c-src expression by the platelets of the CMD patient was comparable to the normal control. These data suggest that: (a) the hyperostosis and the metaphyseal long bone deformity in the present CMD patient might be explained by osteoclast dysfunction due to impaired expression of the osteoclast-reactive vacuolar proton pump; and (b) a protooncogene c-src was not associated with the pathogenesis of the present CMD patient.
authors.affiliation: Department of Pediatrics, Osaka University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: N
authors.initials: N
authors.lastname: Kurihara
authors.forename: K
authors.initials: K
authors.lastname: Yamaoka
authors.forename: K
authors.initials: K
authors.lastname: Ozono
authors.forename: M
authors.initials: M
authors.lastname: Okada
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: S
authors.initials: S
authors.lastname: Matsumoto
authors.forename: T
authors.initials: T
authors.lastname: Michigami
authors.forename: J
authors.initials: J
authors.lastname: Ono
authors.forename: S
authors.initials: S
authors.lastname: Okada
mesh_terms: D001792:Blood Platelets / Q000502:physiology; D015153:Blotting, Western; D001848:Bone Diseases, Developmental / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology*; D001862:Bone Resorption; D001842:Bone and Bones / Q000378:metabolism; D002116:Calcitonin / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology; D002675:Child, Preschool; D016391:Genes, src; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008297:Male; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010281:Parathyroid Hormone / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000097:blood; D017494:Proton Pumps / Q000235:genetics*; D011859:Radiography; D011994:Recombinant Proteins / Q000494:pharmacology; D012886:Skull / Q000000981:diagnostic imaging / Q000473:pathology*; D019379:Teriparatide; D014617:Vacuoles / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D017494:Proton Pumps; D011994:Recombinant Proteins; D019379:Teriparatide; D016173:Macrophage Colony-Stimulating Factor; D002116:Calcitonin; D016392:Proto-Oncogene Proteins pp60(c-src); D002117:Calcitriol