Expression and Localization of Connexin 43 in Cartilage of Horses with Osteochondrosis dissecans
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Osteochondrosis dissecans (OCD) in growing individuals represents a chondrodysplasia with uncertain etiology. Regions of retained cartilage result from retardation of the progression of subchondral ossification (Glaser et al). Focal avascular necrosis is hypothesized to initiate OCD. The molecular events defining OCD, a prevalent developmental joint disease in human and animal, have been limited to the study of a relatively small number of candidate molecules. After examining a large-scale microarray study, two of the most dysregulated genes were Connexin 43 (Cx43), a gap junction protein encoded by the GJAP1 gene, which provides routes for the movement of low-molecular weight materials, and Proteoglycan 4 (PRG4), a surface lubricating protein. Using more advanced quantitative real-time polymerase chain reaction (RT-PCR) method, Cx43 was found to be expressed 7-fold higher in OCD cartilage than normal cartilage, and PRG4 was found to be expressed 3-times lower in OCD cartilage than normal cartilage. Through histological methods of immunohistochemistry and in-situ hybridization, Cx43?s expression and translation were found to be around the area of osteoclasts/ chondroclasts as well as the subchondral bone separation as a result of the OCD lesion with clefting. We hypothesize Cx43 has the ability to attenuate the inflammatory processes and further damage the surrounding tissues. At the same time, PRG4 is down-regulated due to the surrounding inflammatory environment.
Dissertation or Thesis