Involvement of ATP, increase of intracellular calcium and the early expression of c-fos in the repair of rat fetal articular cartilage

Cell Tissue Res. 2004 Aug;317(2):117-28. doi: 10.1007/s00441-004-0893-7. Epub 2004 Jun 15.


To compare the potential of adult and fetal animals to repair articular cartilage, we investigated the early process after creating superficial defects in the femoral knee cartilage in rat models. In fetuses at 19 days of gestation, both chondrocytes and the extracellular matrix responded notably by 48 h after artificial injury. Staining patterns with safranin O revealed that, by 1 h after injury, some components of the extracellular matrix around the wound were modified, and the change spread from the limited region to the entire knee cartilage within 24 h. The chondrocytes in the area surrounding the wound transiently expressed increased level of c-fos from 1 h to 6 h. The wound remained 1 day after birth, i.e., 72 h after injury, but was completely repaired 10 days after birth. In contrast, neither visible responses nor transient c-fos expression was observed in 12-week-old adult articular cartilage 48 h after injury. We also examined the relationships between the intracellular Ca2+ concentration ([Ca2+]i) and the induction of c-fos expression in the cartilage. Applications of ATP or Ca2+ ionophore A23187, both of which increase [Ca2+]i, induced immediate expression of c-fos in primary cultured chondrocytes: 1 microM ATP elicited an increase of [Ca2+]i in chondrocytes in fetal cartilage slices, but 1 mM was required in adult cartilage slices. Our findings show the presence of a signaling pathway that is apparently active in the repair of fetal but not adult articular cartilage and that involves the intercellular transfer of ATP, increase of [Ca2+]i, and expression of c-fos in cartilage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Adenosine Triphosphate / pharmacology
  • Animals
  • Calcimycin / pharmacology
  • Calcium / metabolism*
  • Cartilage, Articular / embryology
  • Cartilage, Articular / injuries
  • Cartilage, Articular / metabolism*
  • Cartilage, Articular / pathology
  • Cells, Cultured
  • Chondrocytes / metabolism*
  • Chondrocytes / pathology
  • Female
  • Fetus / embryology
  • Fetus / metabolism*
  • Fetus / pathology
  • Gene Expression Regulation, Developmental / physiology
  • Ionophores / pharmacology
  • Pregnancy
  • Proto-Oncogene Proteins c-fos / biosynthesis*
  • Rats
  • Rats, Wistar
  • Wound Healing / physiology


  • Ionophores
  • Proto-Oncogene Proteins c-fos
  • Calcimycin
  • Adenosine Triphosphate
  • Calcium