Bone marrow-derived osteoclast-like cells from a patient with craniometaphyseal dysplasia lack expression of osteoclast-reactive vacuolar proton pump

T. Yamamoto, N. Kurihara, K. Yamaoka, K. Ozono, M. Okada, K. Yamamoto, S. Matsumoto, T. Michigami, J. Ono, S. Okada

Research output: Contribution to journalArticle

37 Scopus citations

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 β-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 β, 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 pp60(c-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.

Original languageEnglish (US)
Pages (from-to)362-367
Number of pages6
JournalJournal of Clinical Investigation
Volume91
Issue number1
DOIs
StatePublished - Jan 1 1993

Keywords

  • bone resorption
  • hyperostosis
  • osteotropic growth factors
  • vacuolar proton pump
  • vitronectin β receptor

ASJC Scopus subject areas

  • Medicine(all)

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