Cellular and humoral mechanisms of osteoclast formation and bone resorption in Gorham–Stout disease
- 10 October 2001
- journal article
- case report
- Published by Wiley in The Journal of Pathology
- Vol. 195 (5) , 624-630
- https://doi.org/10.1002/path.989
Abstract
Gorham–Stout disease (GSD) is a rare, massively osteolytic condition which is associated with increased vascularity and an increase in osteoclast numbers. To determine the cellular and humoral mechanisms underlying the increase in osteoclast numbers and osteolysis in GSD, this study analysed circulating osteoclast precursor numbers and sensitivity to osteoclastogenic factors in a GSD patient and age/sex‐matched controls. Monocytes were cultured with M‐CSF (25 ng/ml) and RANKL (30 ng/ml) and osteoclast formation was assessed in terms of the formation of TRAP+ and VNR+ multinucleated cells and the extent of lacunar resorption. There was no increase in the proportion of circulating osteoclast precursors in GSD relative to controls, but lacunar resorption was consistently greater in GSD monocyte cultures. Increased osteoclast formation in GSD was noted when monocytes were incubated with IL‐1β (1 ng/ml), IL‐6/sIL‐6R (100 ng/ml), and TNFα (10 ng/ml). An increase in osteoclast differentiation and bone resorption was also noted in control monocyte cultures in the presence of GSD serum. These results indicate that the increase in osteoclast formation in GSD is due not to an increase in the number of circulating osteoclast precursors, but rather to an increase in the sensitivity of these precursors to humoral factors which promote osteoclast formation and bone resorption. Copyright © 2001 John Wiley & Sons, Ltd.Keywords
This publication has 19 references indexed in Scilit:
- Tumor Necrosis Factor α Stimulates Osteoclast Differentiation by a Mechanism Independent of the Odf/Rankl–Rank InteractionThe Journal of Experimental Medicine, 2000
- The Roles of Osteoprotegerin and Osteoprotegerin Ligand in the Paracrine Regulation of Bone ResorptionJournal of Bone and Mineral Research, 2000
- The Ligand for Osteoprotegerin (OPGL) Directly Activates Mature OsteoclastsThe Journal of cell biology, 1999
- The Gorham-Stout syndrome (Gorham's massive osteolysis)The Journal of Bone and Joint Surgery. British volume, 1999
- Osteoclast Differentiation Factor (ODF) Induces Osteoclast-like Cell Formation in Human Peripheral Blood Mononuclear Cell CulturesBiochemical and Biophysical Research Communications, 1998
- Osteoclast Differentiation Factor Mediates an Essential Signal for Bone Resorption Induced by 1α,25-Dihydroxyvitamin D3, Prostaglandin E2, or Parathyroid Hormone in the Microenvironment of BoneBiochemical and Biophysical Research Communications, 1998
- The human osteoclast precursor circulates in the monocyte fractionEndocrinology, 1996
- Interleukin-6: a potential mediator of the massive osteolysis in patients with Gorham-Stout diseaseJournal of Clinical Endocrinology & Metabolism, 1996
- Macrophage colony-stimulating factor is indispensable for both proliferation and differentiation of osteoclast progenitors.Journal of Clinical Investigation, 1993
- Immunophenotypic differences between osteoclasts and macrophage polykaryons: immunohistological distinction and implications for osteoclast ontogeny and function.Journal of Clinical Pathology, 1990