Bone Cells From Patients With Quiescent Crohn's Disease Show a Reduced Growth Potential and an Impeded Maturation

Angela E. Oostlander, Nathalie Bravenhoer*, Huib W. van Essen, Jenneke Klein-Nulend, Willem F. Lems, Bert A. J. M. Schulten, Gerard Dijkstra, C. Janneke van der Woude, Ad A. van Bodegraven, Paul Lips, Dutch Initiative on Crohn and Colitis

*Corresponding author for this work

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Abstract

Patients with Crohn's disease (CD) are at increased risk of developing osteoporosis. The mechanism underlying bone loss in CD patients is only partly understood. Inflammation is thought to contribute by causing a disturbed bone remodeling. In this study, we aimed to compare functional characteristics of osteoblasts from CD patients and controls, as osteoblasts are one of the effector cells in bone remodeling. The study included 18 patients with quiescent CD and 18 healthy controls. Bone cells obtained from iliac crest biopsies were cultured in the absence and presence of the inflammatory cytokines IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, IL-10, and TGF-beta. At various time points, cell proliferation and differentiation were analyzed. Bone cells from CD patients showed a prolonged culture period to reach confluence and a decreased cell number at confluence. CD patient-derived bone cell cultures produced higher alkaline phosphatase levels, whereas osteocalcin levels were considerably reduced compared to control cultures. At the proliferation level, the responsiveness to inflammatory cytokines was similar in bone cells from CD patients and controls. At the differentiation level, CD cultures showed an increased responsiveness to IL-6 and a decreased responsiveness to TGF-beta. Responsiveness to the other cytokines tested was unaffected. In summary, we show a reduced growth potential and impeded maturation of bone cells from quiescent CD patients in vitro. These disease-related alterations combined with an unchanged sensitivity of CD patient-derived bone cells to inflammatory cytokines, provide a new insight in the understanding of CD-associated bone loss. J. Cell. Biochem. 113: 2424-2431, 2012. (C) 2012 Wiley Periodicals, Inc.

Original languageEnglish
Pages (from-to)2424-2431
Number of pages8
JournalJournal of Cellular Biochemistry
Volume113
Issue number7
DOIs
Publication statusPublished - Jul-2012

Keywords

  • INFLAMMATORY BOWEL DISEASE
  • OSTEOBLASTS
  • PROLIFERATION
  • DIFFERENTIATION
  • CYTOKINES
  • INFLAMMATORY-BOWEL-DISEASE
  • NECROSIS-FACTOR-ALPHA
  • IN-VITRO
  • OSTEOBLAST DIFFERENTIATION
  • MINERAL DENSITY
  • METHOTREXATE
  • INTERLEUKIN-6
  • MECHANISM

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