title: Soluble signalling factors derived from differentiated cartilage tissue affect chondrogenic differentiation of rat adult marrow stromal cells.
abstract: BACKGROUND
  Chondral defects show lack of proper regeneration whereas osteochondral lesions display limited regeneration capacity. Latter is probably due to immigration of chondroprogenitor cells from the subchondral bone. Known chondroprogenitor cells for cartilage tissues are multi-potent adult marrow stromal or mesenchymal stem cells (MSCs). In vitro chondrogenic differentiation of these precursor cells usually require cues from growth and signalling factors provided in vivo by surrounding tissues and cells. We hypothesise that signalling factors secreted by differentiated cartilage tissue can initiate and maintain chondrogenic differentiation status of MSCs.
  
  
  METHODS
  To study such paracrine communication between allogenic rat articular cartilage and rat MSCs embedded in alginate beads a novel coculture system without addition of external growth factors has been established.
  
  
  RESULTS
  Impact of cartilage on differentiating MSCs was observed at two different time points. Firstly, sustained expression of Sox9 was observed at an early stage which indicated induction of chondrogenic differentiation. Secondly, late stage repression of collagen X indicated pre-hypertrophic arrest of differentiation. In the culture supernatant we have identified vascular endothelial growth factor alpha (VEGF-164 alpha), matrix metalloproteinase (MMP) -13 and tissue inhibitors of MMPs (TIMP-1 and TIMP-2) which could be traced back either to the cartilage explant or to the MSCs under the influence of cartilage.
  
  
  CONCLUSIONS
  The identified factors might be involved in regulation of collagen X gene and protein expression and therefore, may have an impact on the control and regulation of MSCs differentiation.
authors.affiliation: Department of Orthopaedic Surgery, Experimental Orthopaedics, University Hospital of Regensburg, Regensburg, Germany.
authors.forename: Nazish
authors.initials: N
authors.lastname: Ahmed
authors.forename: Rita
authors.initials: R
authors.lastname: Dreier
authors.forename: Achim
authors.initials: A
authors.lastname: Göpferich
authors.forename: Joachim
authors.initials: J
authors.lastname: Grifka
authors.forename: Susanne
authors.initials: S
authors.lastname: Grässel
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002356:Cartilage / Q000166:cytology* / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D020219:Chondrogenesis; D018920:Coculture Techniques; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006609:High Mobility Group Proteins / Q000235:genetics; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008954:Models, Biological; D051381:Rats; D055758:SOX9 Transcription Factor; D015398:Signal Transduction; D012995:Solubility; D017154:Stromal Cells / Q000166:cytology*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D006609:High Mobility Group Proteins; D055758:SOX9 Transcription Factor; D014157:Transcription Factors; D019716:Tissue Inhibitor of Metalloproteinase-2; D003094:Collagen; D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2