title: Characterization of an Ex vivo Femoral Head Model Assessed by Markers of Bone and Cartilage Turnover.
abstract: OBJECTIVE
  The pathophysiology of osteoarthritis involves the whole joint and is characterized by cartilage degradation and altered subchondral bone turnover. At present, there is a need for biological models that allow investigation of the interactions between the key cellular players in bone/cartilage: osteoblasts, osteoclasts, and chondrocytes.
  
  
  METHODS
  Femoral heads from 3-, 6-, 9-, and 12-week-old female mice were isolated and cultured for 10 days in serum-free media in the absence or presence of IGF-I (100 nM) (anabolic stimulation) or OSM (10 ng/mL) + TNF-α (20 ng/mL) (catabolic stimulation). Histology on femoral heads before and after culture was performed, and the growth plate size was examined to evaluate the effects on cell metabolism. The conditioned medium was examined for biochemical markers of bone and cartilage degradation/formation.
  
  
  RESULTS
  Each age group represented a unique system regarding the interest of bone or cartilage metabolism. Stimulation over 10 days with OSM + TNF-α resulted in depletion of proteoglycans from the cartilage surface in all ages. Furthermore, OSM + TNF-α decreased growth plate size, whereas IGF-I increased the size. Measurements from the conditioned media showed that OSM + TNF-α increased the number of osteoclasts by approximately 80% and induced bone and cartilage degradation by approximately 1200% and approximately 2600%, respectively. Stimulation with IGF-I decreased the osteoclast number and increased cartilage formation by approximately 30%.
  
  
  CONCLUSIONS
  Biochemical markers and histology together showed that the catabolic stimulation induced degradation and the anabolic stimulation induced formation in the femoral heads. We propose that we have established an explant whole-tissue model for investigating cell-cell interactions, reflecting parts of the processes in the pathogenesis of joint degenerative diseases.
authors.affiliation: Cartilage Biology and Biomarkers R&D, Nordic Bioscience A/S, Herlev, Denmark.
authors.forename: Suzi Hoegh
authors.initials: SH
authors.lastname: Madsen
authors.affiliation: Cartilage Biology and Biomarkers R&D, Nordic Bioscience A/S, Herlev, Denmark.
authors.forename: Anne Sofie
authors.initials: AS
authors.lastname: Goettrup
authors.affiliation: Cartilage Biology and Biomarkers R&D, Nordic Bioscience A/S, Herlev, Denmark.
authors.forename: Gedske
authors.initials: G
authors.lastname: Thomsen
authors.affiliation: Department of Molecular Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Søren Tvorup
authors.initials: ST
authors.lastname: Christensen
authors.affiliation: Cartilage Biology and Biomarkers R&D, Nordic Bioscience A/S, Herlev, Denmark.
authors.forename: Nikolaj
authors.initials: N
authors.lastname: Schultz
authors.affiliation: Bone Biology R&D, Nordic Bioscience A/S, Herlev, Denmark.
authors.forename: Kim
authors.initials: K
authors.lastname: Henriksen
authors.affiliation: Cartilage Biology and Biomarkers R&D, Nordic Bioscience A/S, Herlev, Denmark.
authors.forename: Anne-Christine
authors.initials: AC
authors.lastname: Bay-Jensen
authors.affiliation: Cartilage Biology and Biomarkers R&D, Nordic Bioscience A/S, Herlev, Denmark.
authors.forename: Morten Asser
authors.initials: MA
authors.lastname: Karsdal
keywords: IGF-I; cytokines; ex vivo; femoral head; growth plate; osteoarthritis