Articular Cartilage Stem Cells

Pain, loss of mobility, and osteoarthritis resulting from injured articular cartilage are a major limiting variable in the athletic careers of racehorses with substantial economic consequences for owners and the racing industry. Unfortunately, the intrinsic repair capacity of mammalian articular cartilage is extremely limited, making therapeutic treatment of articular cartilage injuries challenging and the prognosis guarded. Despite recent advances in surgical and pharmacological treatment options, damaged adult articular cartilage is never fully restored. Instead, a structurally different and functionally deficient "hyaline-like" scar tissue forms in place of pre-existing articular cartilage. In contrast to mammals, we have recently determined that the axolotl salamander has a remarkable ability to fully repair even large joint surface lesions and fully restore normal articular cartilage cellularity and structure. These vertebrate animals retain a tissue in the intra-articular space of adults that appears to be morphologically similar to a mesenchymal tissue that is present only transiently during fetal life in the developing synovial joint of mammals. This proposal requests support to study the fetal "interzone" tissue of horses and determine if it is homologous to the adult "interzone-like" tissue ofaxolotls. Molecular and cell biology methods will be used to compare these tissues in the two species and test the hypothesis that equine interzone tissue contains progenitor "stem" cells for articular chondrocytes.