title: Glucocorticoids exert context-dependent effects on cells of the joint in vitro.
abstract: BACKGROUND
  Glucocorticoids are known to attenuate bone formation in vivo leading to decreased bone volume and increased risk of fractures, whereas effects on the joint tissue are less characterized. However, glucocorticoids appear to have a reducing effect on inflammation and pain in osteoarthritis. This study aimed at characterizing the effect of glucocorticoids on chondrocytes, osteoclasts, and osteoblasts.
  
  
  METHODS
  We used four model systems to investigate how glucocorticoids affect the cells of the joint; two intact tissues (femoral head- and cartilage-explants), and two separate cell cultures of osteoblasts (2T3-pre-osteoblasts) and osteoclasts (CD14(+)-monocytes). The model systems were cultured in the presence of two glucocorticoids; prednisolone or dexamethasone. To induce anabolic and catabolic conditions, cultures were activated by insulin-like growth factor I/bone morphogenetic protein 2 and oncostatin M/tumor necrosis factor-α, respectively. Histology and markers of bone- and cartilage-turnover were used to evaluate effects of glucocorticoid treatment.
  
  
  RESULTS
  Prednisolone treatment decreased collagen type-II degradation in immature cartilage, whereas glucocorticoids did not affect collagen type-II in mature cartilage. Glucocorticoids had an anti-catabolic effect on catabolic-activated cartilage from a bovine stifle joint and murine femoral heads. Glucocorticoids decreased viability of all bone cells, leading to a reduction in osteoclastogenesis and bone resorption; however, bone morphogenetic protein 2-stimulated osteoblasts increased bone formation, as opposed to non-stimulated osteoblasts.
  
  
  CONCLUSIONS
  Using highly robust in vitro models of bone and cartilage turnover, we suggest that effects of glucocorticoids highly depend on the activation and differential stage of the cell targeted in the joint. Present data indicated that glucocorticoid treatment may be beneficial for articular cartilage, although detrimental effects on bone should be taken into account.
authors.affiliation: Cartilage Biology and Biomarkers, Nordic Bioscience A/S, Herlev Hovedgade 207, DK-2730 Herlev, Denmark. shm@nordicbioscience.com
authors.forename: Suzi H
authors.initials: SH
authors.lastname: Madsen
authors.forename: Kim V
authors.initials: KV
authors.lastname: Andreassen
authors.forename: Søren T
authors.initials: ST
authors.lastname: Christensen
authors.forename: Morten A
authors.initials: MA
authors.lastname: Karsdal
authors.forename: Francis M
authors.initials: FM
authors.lastname: Sverdrup
authors.forename: Anne-Christine
authors.initials: AC
authors.lastname: Bay-Jensen
authors.forename: Kim
authors.initials: K
authors.lastname: Henriksen
mesh_terms: D000818:Animals; D016723:Bone Remodeling / Q000187:drug effects; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005270:Femur Head / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007596:Joints / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D051379:Mice; D009928:Organ Specificity; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011239:Prednisolone / Q000494:pharmacology
chemical_list: D016207:Cytokines; D005938:Glucocorticoids; D018950:Lipopolysaccharide Receptors; D003907:Dexamethasone; D011239:Prednisolone