title: The role of osteoblast cells in the pathogenesis of unicameral bone cysts.
abstract: OBJECTIVE
  The pathogenesis of unicameral bone cysts (UBCs) remains largely unknown. Osteoclasts have been implicated, but the role of osteoblastic cells has, to date, not been explored. This study investigated the pathophysiology of UBCs by examining the interactions between the cyst fluid and human bone marrow stromal cells (hBMSCs) and the effect of the fluid on osteogenesis.
  
  
  METHODS
  Fluid was aspirated from two UBCs and analysed for protein, electrolyte and cytokine levels. Graded concentrations of the fluid were used as culture media for hBMSCs to determine the effects of the fluid on hBMSC proliferation and osteogenic differentiation. The fibrocellular lining was analysed histologically and by electron microscopy.
  
  
  RESULTS
  Alkaline phosphatase (ALP) staining of hBMSCs that were cultured in cyst fluid demonstrated increased cell proliferation and osteogenic differentiation compared to basal media controls. Biochemical analysis of these hBMSCs compared to basal controls confirmed a marked increase in DNA content (as a marker of proliferation) and ALP activity (as a marker of osteogenic differentiation) which was highly significant (p < 0.001). Osteoclasts were demonstrated in abundance in the cyst lining. The cyst fluid cytokine profile revealed levels of the pro-osteoclast cytokines IL-6, MIP-1α and MCP-1 that were 19×, 31× and 35× greater than those in reference serum.
  
  
  CONCLUSIONS
  Cyst fluid promoted osteoblastic growth and differentiation. Despite appearing paradoxical that the cyst fluid promoted osteogenesis, osteoblastic cells are required for osteoclastogenesis through RANKL signalling. Three key cytokines in this pathway (IL-6, MIP-1α, MCP-1) were highly elevated in cyst fluid. These findings may hold the key to the pathogenesis of UBCs, with implications for treatment methods.
authors.affiliation: Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton School of Medicine, Tremona Road, Southampton, SO16 6YD UK ; Department of Paediatric Orthopaedics, University Hospital Southampton, Tremona Road, Southampton, SO16 6YD UK.
authors.forename: Alexander
authors.initials: A
authors.lastname: Aarvold
authors.forename: James O
authors.initials: JO
authors.lastname: Smith
authors.forename: Edward R
authors.initials: ER
authors.lastname: Tayton
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Edwards
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Fowler
authors.forename: Edward D
authors.initials: ED
authors.lastname: Gent
authors.forename: Richard O C
authors.initials: RO
authors.lastname: Oreffo
keywords: Cytokine; Osteoblast cell; Osteoclast; RANK ligand; Unicameral bone cyst
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