Abnormalities in osteoclast precursors and marrow accessory cells in Paget's disease

Anne Demulder, Shunji Takahashi, Frederick R. Singer, David J. Hosking, G. David Roodman

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Paget's disease of bone is characterized by increased numbers of abnormal osteoclasts. To determine if osteoclast precursors were increased or abnormal in this disease, we examined CFU-GM, the committed granulocyte-macrophage progenitor and the most likely precursor for osteoclasts. In cultures of unfractionated marrow mononuclear cells, CFU-GM colony formation was significantly increased in Paget's marrow cultures compared to that in normal cells (356 ± 44 us. 271 ± 15/105 cells; P <0.05). However, when we enriched hematopoietic precursors from Paget's and normal marrow samples using an antibody that recognizes the CD34 antigen present on most hematopoietic precursors, we found that similar numbers of CFU-GM colonies were formed (87 ± 13/104 cells plated vs. 83 ± 13). Coculture experiments with highly purified hematopoietic precursors (CD34+ cells) and non-hematopoietic marrow accessory cells (CD34- cells) revealed that the growth of Paget's precursors was significantly enhanced above expected levels by normal or Pagetic CD34- cells (P <0.05). CFU-GM colony formation was also significantly enhanced when normal CD34+ cells were cocultured with Pagetic, but not with normal, CD34- cells. In addition, CFU-GM colony-derived cells from Paget's patients were hyperresponsive to 1,25-dihydroxyvitamin D3 and could form osteoclast-like multinucleated cells with 1,25-dihydroxyvitamin D3 concentrations one tenth of that required for normal multinucleated formation (10-11 vs. 10-10 M). These data suggest that osteoclast precursors may be abnormal in Paget's disease, and other cells in the Pagetic marrow microenvironment may further enhance the growth and differentiation of these abnormal precursors.

Original languageEnglish (US)
Pages (from-to)1978-1982
Number of pages5
JournalEndocrinology
Volume133
Issue number5
StatePublished - Nov 1993
Externally publishedYes

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Osteoclasts
Bone Marrow
Granulocyte-Macrophage Progenitor Cells
Calcitriol
CD34 Antigens
Osteitis Deformans
Growth
Coculture Techniques

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Demulder, A., Takahashi, S., Singer, F. R., Hosking, D. J., & Roodman, G. D. (1993). Abnormalities in osteoclast precursors and marrow accessory cells in Paget's disease. Endocrinology, 133(5), 1978-1982.

Abnormalities in osteoclast precursors and marrow accessory cells in Paget's disease. / Demulder, Anne; Takahashi, Shunji; Singer, Frederick R.; Hosking, David J.; Roodman, G. David.

In: Endocrinology, Vol. 133, No. 5, 11.1993, p. 1978-1982.

Research output: Contribution to journalArticle

Demulder, A, Takahashi, S, Singer, FR, Hosking, DJ & Roodman, GD 1993, 'Abnormalities in osteoclast precursors and marrow accessory cells in Paget's disease', Endocrinology, vol. 133, no. 5, pp. 1978-1982.
Demulder A, Takahashi S, Singer FR, Hosking DJ, Roodman GD. Abnormalities in osteoclast precursors and marrow accessory cells in Paget's disease. Endocrinology. 1993 Nov;133(5):1978-1982.
Demulder, Anne ; Takahashi, Shunji ; Singer, Frederick R. ; Hosking, David J. ; Roodman, G. David. / Abnormalities in osteoclast precursors and marrow accessory cells in Paget's disease. In: Endocrinology. 1993 ; Vol. 133, No. 5. pp. 1978-1982.
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