Enhanced RANK ligand expression and responsivity of bone marrow cells in Paget's disease of bone

Cheikh Menaa, Sakamuri V. Reddy, Noriyoshi Kurihara, Hidefumi Maeda, Dirk Anderson, Tim Cundy, Jillian Cornish, Frederick R. Singer, Jan M. Bruder, G. David Roodman

Research output: Contribution to journalArticle

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Abstract

Paget's disease is characterized by highly localized areas of increased osteoclast (OCL) activity. This suggests that the microenvironment in pagetic lesions is highly osteoclastogenic, or that OCL precursors in these lesions are hyperresponsive to osteoclastogenic factors (or both). To examine these possibilities, we compared RANK ligand (RANKL) mRNA expression in a marrow stromal cell line developed from a pagetic lesion (PSV10) with that in a normal stromal cell line (Saka), and expression in marrow samples from affected bones of Paget's patients with that in normal marrow. RANKL mRNA was increased in PSV10 cells and pagetic marrow compared with Saka cells and normal marrow, and was also increased in marrow from affected bones compared with uninvolved bones from Paget's patients. Furthermore, pagetic marrow cells formed OCLs at much lower RANKL concentrations than did normal marrow. Anti-IL-6 decreased the RANKL responsivity of pagetic marrow to normal levels, whereas addition of IL-6 to normal marrow enhanced RANKL responsivity. Thus, RANKL expression and responsivity is increased in pagetic lesions, in part mediated by IL-6. These data suggest that the combination of enhanced expression of RANKL in affected bones and increased RANKL sensitivity of pagetic OCL precursors may contribute to the elevated numbers of OCLs in Paget's disease.

Original languageEnglish (US)
Pages (from-to)1833-1838
Number of pages6
JournalJournal of Clinical Investigation
Volume105
Issue number12
StatePublished - 2000
Externally publishedYes

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RANK Ligand
Osteitis Deformans
Bone Marrow Cells
Bone Marrow
Osteoclasts
Interleukin-6
Stromal Cells
Bone and Bones
Cell Line
Messenger RNA

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Enhanced RANK ligand expression and responsivity of bone marrow cells in Paget's disease of bone. / Menaa, Cheikh; Reddy, Sakamuri V.; Kurihara, Noriyoshi; Maeda, Hidefumi; Anderson, Dirk; Cundy, Tim; Cornish, Jillian; Singer, Frederick R.; Bruder, Jan M.; Roodman, G. David.

In: Journal of Clinical Investigation, Vol. 105, No. 12, 2000, p. 1833-1838.

Research output: Contribution to journalArticle

Menaa, C, Reddy, SV, Kurihara, N, Maeda, H, Anderson, D, Cundy, T, Cornish, J, Singer, FR, Bruder, JM & Roodman, GD 2000, 'Enhanced RANK ligand expression and responsivity of bone marrow cells in Paget's disease of bone', Journal of Clinical Investigation, vol. 105, no. 12, pp. 1833-1838.
Menaa, Cheikh ; Reddy, Sakamuri V. ; Kurihara, Noriyoshi ; Maeda, Hidefumi ; Anderson, Dirk ; Cundy, Tim ; Cornish, Jillian ; Singer, Frederick R. ; Bruder, Jan M. ; Roodman, G. David. / Enhanced RANK ligand expression and responsivity of bone marrow cells in Paget's disease of bone. In: Journal of Clinical Investigation. 2000 ; Vol. 105, No. 12. pp. 1833-1838.
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AU - Cornish, Jillian

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