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

Takehisa Yamamoto, Noriyoshi Kurihara, Kanji Yamaoka, Keiichi Ozono, Masato Okada, Katsusuke Yamamoto, Sayuri Matsumoto, Toshimi Michigami, Jiro Ono, Shintaro Okada

Research output: Contribution to journalArticle

37 Citations (Scopus)

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 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 (A) 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
StatePublished - Jan 1993
Externally publishedYes

Fingerprint

Proton Pumps
Osteoclasts
Bone Marrow
Hyperostosis
Bone and Bones
salmon calcitonin
Monoclonal Antibodies
Bone Marrow Cells
Vitronectin Receptors
Developmental Bone Disease
Sperm Whale
Macrophage Colony-Stimulating Factor
Schwartz-Lelek syndrome
Calcitriol
Dentin
Interleukin-1
Interleukin-6
Blood Platelets
Western Blotting
Biopsy

Keywords

  • Bone resorption
  • Hyperostosis
  • Osteotropic growth factors
  • Vacuolar proton pump
  • Vitronectin β receptor

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Bone marrow-derived osteoclast-like cells from a patient with craniometaphyseal dysplasia lack expression of osteoclast-reactive vacuolar proton pump. / Yamamoto, Takehisa; Kurihara, Noriyoshi; Yamaoka, Kanji; Ozono, Keiichi; Okada, Masato; Yamamoto, Katsusuke; Matsumoto, Sayuri; Michigami, Toshimi; Ono, Jiro; Okada, Shintaro.

In: Journal of Clinical Investigation, Vol. 91, No. 1, 01.1993, p. 362-367.

Research output: Contribution to journalArticle

Yamamoto, T, Kurihara, N, Yamaoka, K, Ozono, K, Okada, M, Yamamoto, K, Matsumoto, S, Michigami, T, Ono, J & Okada, S 1993, 'Bone marrow-derived osteoclast-like cells from a patient with craniometaphyseal dysplasia lack expression of osteoclast-reactive vacuolar proton pump', Journal of Clinical Investigation, vol. 91, no. 1, pp. 362-367.
Yamamoto, Takehisa ; Kurihara, Noriyoshi ; Yamaoka, Kanji ; Ozono, Keiichi ; Okada, Masato ; Yamamoto, Katsusuke ; Matsumoto, Sayuri ; Michigami, Toshimi ; Ono, Jiro ; Okada, Shintaro. / Bone marrow-derived osteoclast-like cells from a patient with craniometaphyseal dysplasia lack expression of osteoclast-reactive vacuolar proton pump. In: Journal of Clinical Investigation. 1993 ; Vol. 91, No. 1. pp. 362-367.
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AU - Okada, Masato

AU - Yamamoto, Katsusuke

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