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Developmental Progenitor Cells of Articular Chondrocytes
Articular cartilage lesions frequently compromise diarthrodial joint function and limit the performance potential of equine athletes. Cartilage is a tissue with poor intrinsic repair capabilities, a primary reason why degenerative joint disease is often progressive. New cell-based therapeutic strategies for equine joint surface injuries are generating a high level of interest. Unfortunately, fibrocartilage formation and poor anchoring of the repair tissue into the surrounding healthy tissue continue to be major challenges. Based on structural and molecular comparisons of different cartilaginous tissues and studies using primary chondrocyte cultures, it is clear that not all chondrocytes are equivalent on a cell biology level. We are trying to advance cell-based therapies for joint surface lesions by considering the unique phenotype that defines normal articular chondrocytes relative to other chondrocyte cell types, as well as the developmental processes that generate these cells. During limb formation, a morphologically distinct zone of cells in the prechondrogenic mesenchyme initiates synovial joint formation. This mesenchymal tissue is known as the “interzone” and appears as a flattened layer of cells connected by gap junctions. Interzone cells exist during early fetal development in all mammals including horses, but are present only transiently prior to joint space cavitation. In a developmental biology context, the interzone is the normal progenitor of all synovial joint tissues including articular cartilage. Using an amphibian model system, we have demonstrated that interzone tissue can facilitate a remarkable repair of large articular cartilage defects and even generate an entirely new diarthrodial joint de novo. More recently, we have been able to characterize interzone tissue in early equine fetuses and isolate primary horse interzone cells that can be expanded in culture. Experiments are being conducted to compare gene expression profiles of interzone cells to different types of chondrocytes on a transcriptome level, while also studying their response to differentiation stimuli. We believe that interzone tissue represents a cell population already developmentally positioned to form articular cartilage – true progenitor cells of articular chondrocytes. As such, they may represent a far superior cell type to focus on for optimizing cell-based therapies to repair articular cartilage defects in the horse.
Keywords: Horse, Cartilage, Interzone