title: DCC is expressed in a CD166-positive subpopulation of chondrocytes in human osteoarthritic cartilage and modulates CRE activity.
abstract: OBJECTIVE
  In a recent study we determined a strong differential expression of DCC in OA compared to normal chondrocytes and a strong impact of the DCC receptor on cellular mobility triggered by its ligand Netrin-1. Migration of chondrocytes or their progenitor cells may play a role in remodeling of cartilage and pathological conditions. The purpose of this study is to identify subsets of chondrocytes expressing DCC and to understand signaling pathways used by DCC in chondrocytes.
  
  
  METHODS
  Immunofluorescent histology of human cartilage was used to determine the expression pattern of CD166, DCC and p-CREB. Cell culture of chondrocytes and SW1353, transient transfection, siRNA transfection, EMSA, luciferase assay, quantitative RT-PCR, ELISA, and Western Blotting were used to study signaling down-stream of DCC.
  
  
  RESULTS
  DCC expressing chondrocytes are mainly located in the surface layers of OA cartilage. These also express CD166 indicating that DCC expressing chondrocytes are progenitor cells. Interestingly, expression of DCC reduces cAMP levels, CREB DNA-binding activity and CRE activity in chondrocytes, whereas down-regulation of DCC results in induction of CRE signaling.
  
  
  CONCLUSIONS
  In summary, DCC is up-regulated in CD166-positive chondrogenic progenitor cells in OA and induces down-regulation of CREB. These findings indicate that migration of CD166 positive progenitor cells to sites of cartilage damage may be directed by regulation of DCC signaling.
authors: Institute of Pathology, University of Regensburg Regensburg, Germany.
authors: Anja-Katrin
authors: AK
authors: Bosserhoff
authors: Institute of Pathology, University of Regensburg Regensburg, Germany.
authors: Simone
authors: S
authors: Hofmeister
authors: Institute of Pathology, University of Regensburg Regensburg, Germany.
authors: Anke
authors: A
authors: Ruedel
authors: Institute of Applied Pathology Speyer, Germany.
authors: Thomas
authors: T
authors: Schubert
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism*; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D000075389:DCC Receptor; D005326:Fetal Proteins / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D020410:Activated-Leukocyte Cell Adhesion Molecule
chemical_list: D015703:Antigens, CD; D015816:Cell Adhesion Molecules, Neuronal; D000242:Cyclic AMP; D017362:Cyclic AMP Response Element-Binding Protein; D000075389:DCC Receptor; D005326:Fetal Proteins; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; C105613:ALCAM protein, human; D020410:Activated-Leukocyte Cell Adhesion Molecule; C115163:CREB1 protein, human; C501909:DCC protein, human
keywords: CRE activity; CREB; DCC; Repellent factors; migration; osteoarthritis