title: Interleukin-1 inhibits osmotically induced calcium signaling and volume regulation in articular chondrocytes.
abstract: OBJECTIVE
  Articular chondrocytes respond to osmotic stress with transient changes in cell volume and the intracellular concentration of calcium ion ([Ca(2+)](i)). The goal of this study was to examine the hypothesis that interleukin-1 (IL-1), a pro-inflammatory cytokine associated with osteoarthritis, influences osmotically induced Ca(2+) signaling.
  
  
  METHODS
  Fluorescence ratio imaging was used to measure [Ca(2+)](i) and cell volume in response to hypo- or hyper-osmotic stress in isolated porcine chondrocytes, with or without pre-exposure to 10-ng/ml IL-1alpha. Inhibitors of IL-1 (IL-1 receptor antagonist, IL-1Ra), Ca(2+) mobilization (thapsigargin, an inhibitor of Ca-ATPases), and cytoskeletal remodeling (toxin B, an inhibitor of the Rho family of small GTPases) were used to determine the mechanisms involved in increased [Ca(2+)](i), F-actin remodeling, volume adaptation and active volume recovery.
  
  
  RESULTS
  In response to osmotic stress, chondrocytes exhibited transient increases in [Ca(2+)](i), generally followed by decaying oscillations. Pre-exposure to IL-1 significantly inhibited regulatory volume decrease (RVD) following hypo-osmotic swelling and reduced the change in cell volume and the time to peak [Ca(2+)](i) in response to hyper-osmotic stress, but did not affect the peak magnitudes of [Ca(2+)](i) in those cells that did respond. Co-treatment with IL-1Ra, thapsigargin, or toxin B restored these responses to control levels. The effects were associated with alterations in F-actin organization.
  
  
  CONCLUSIONS
  IL-1 alters the normal volumetric and Ca(2+) signaling response of chondrocytes to osmotic stress through mechanisms involving F-actin remodeling via small Rho GTPases. These findings provide further insights into the mechanisms by which IL-1 may interfere with normal physiologic processes in the chondrocyte, such as the adaptation or regulatory responses to mechanical or osmotic loading.
authors.affiliation: Departments of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: S
authors.initials: S
authors.lastname: Pritchard
authors.forename: B J
authors.initials: BJ
authors.lastname: Votta
authors.forename: S
authors.initials: S
authors.lastname: Kumar
authors.forename: F
authors.initials: F
authors.lastname: Guilak
mesh_terms: D000199:Actins / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D002358:Cartilage, Articular / Q000378:metabolism*; D048429:Cell Size; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000378:metabolism*; D009995:Osmosis / Q000502:physiology; D009997:Osmotic Pressure; D010003:Osteoarthritis / Q000378:metabolism / Q000503:physiopathology; D015398:Signal Transduction
chemical_list: D000199:Actins; D007375:Interleukin-1; D002118:Calcium