Developmental Aspects of Pagetic Osteoclasts

Deborah L. Galson, Quanhong Sun, G. David Roodman

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Paget's disease of bone (PDB) affects 1-2 million Americans. The primary lesion in PDB is the formation of abnormal osteoclasts (OCL), which leads to highly localized bone resorption accompanied by exuberant new bone formation that is of poor quality. The OCL are increased in number and size, including increased nuclei/OCL, and express a "pagetic phenotype" that distinguishes them from normal OCL. Pagetic OCL precursors form OCL more quickly and at lower levels of inducers of OCL differentiation, including receptor activator of nuclear factor kappa-B ligand, tumor necrosis factor ?, and 1,25-(OH)2D3. Another aspect of the pagetic OCL phenotype is the increased expression and secretion of the cytokine interleukin-6, which plays a large role in the development of pagetic OCL. Further, a number of key internal signaling molecules and transcription factors are altered in both pagetic OCL precursors and pagetic OCL. Lastly, pagetic OCL express increased coupling factors to promote osteoblastic differentiation. OCLs in PDB play a critical role in the enhanced osteoblast activity in PDB, since therapies targeting OCLs decrease new bone formation and induce clinical remission in PDB.

Original languageEnglish (US)
Title of host publicationAdvances in Pathobiology and Management of Paget's Disease of Bone
PublisherElsevier Inc.
Pages37-53
Number of pages17
ISBN (Electronic)9780128096901
ISBN (Print)9780128050835
DOIs
StatePublished - May 9 2016

Fingerprint

Osteoclasts
Osteitis Deformans
Osteogenesis
RANK Ligand
Phenotype
Bone Resorption
Osteoblasts
Interleukin-6
Transcription Factors
Tumor Necrosis Factor-alpha
Cytokines

Keywords

  • Measles virus nucleocapsid protein
  • Osteoblasts
  • Osteoclasts
  • P62
  • Paget's disease
  • Sequestosome-1

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Galson, D. L., Sun, Q., & Roodman, G. D. (2016). Developmental Aspects of Pagetic Osteoclasts. In Advances in Pathobiology and Management of Paget's Disease of Bone (pp. 37-53). Elsevier Inc.. https://doi.org/10.1016/B978-0-12-805083-5.00004-X

Developmental Aspects of Pagetic Osteoclasts. / Galson, Deborah L.; Sun, Quanhong; Roodman, G. David.

Advances in Pathobiology and Management of Paget's Disease of Bone. Elsevier Inc., 2016. p. 37-53.

Research output: Chapter in Book/Report/Conference proceedingChapter

Galson, DL, Sun, Q & Roodman, GD 2016, Developmental Aspects of Pagetic Osteoclasts. in Advances in Pathobiology and Management of Paget's Disease of Bone. Elsevier Inc., pp. 37-53. https://doi.org/10.1016/B978-0-12-805083-5.00004-X
Galson DL, Sun Q, Roodman GD. Developmental Aspects of Pagetic Osteoclasts. In Advances in Pathobiology and Management of Paget's Disease of Bone. Elsevier Inc. 2016. p. 37-53 https://doi.org/10.1016/B978-0-12-805083-5.00004-X
Galson, Deborah L. ; Sun, Quanhong ; Roodman, G. David. / Developmental Aspects of Pagetic Osteoclasts. Advances in Pathobiology and Management of Paget's Disease of Bone. Elsevier Inc., 2016. pp. 37-53
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