Atypical multinucleated cells form in long-term marrow cultures from patients with Paget's disease

A. Kukita, C. Chenu, L. M. McManus, G. R. Mundy, G. D. Roodman

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

Although Paget's disease is the most flagrant example of a primary osteoclast disorder, little is known of osteoclast biology in this disease. In this report we have studied the formation of cells with the osteoclast phenotype in long-term cultures of marrow mononuclear cells derived from patients with Paget's disease, and compared these with similar cells formed in long-term marrow cultures from normal individuals, and with osteoclasts present in pagetic bone. Osteoclasts formed in pagetic marrow cultures resembled osteoclasts present in pagetic bone, but were distinctly different from osteoclasts formed in normal marrow cultures. Osteoclast formation was 10-20-fold greater in pagetic marrow cultures than in normal cultures. The multinucleated cells formed in cultures of pagetic marrow were much larger in size, were hyperresponsive to 1,25(OH)2 vitamin D, had more nuclei per cell, had increased levels of tartrate-resistant acid phosphatase activity and had ultrastructural features which were not seen in multinucleated cells formed from normal marrow mononuclear cells. These pagetic marrow-derived multinucleated cells formed large resorption lacunae on calcified matrices and cross-reacted with monoclonal antibodies which preferentially bind to osteoclasts. The multinucleated cells formed from marrow obtained from uninvolved sites in Paget's patients also displayed these abnormal features.

Original languageEnglish (US)
Pages (from-to)1280-1286
Number of pages7
JournalJournal of Clinical Investigation
Volume85
Issue number4
DOIs
StatePublished - 1990

Keywords

  • Paget's disease
  • bone marrow cultures
  • osteoclasts

ASJC Scopus subject areas

  • Medicine(all)

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