Submitted to: International Conference on Production Diseases in Farm Animals
Publication Type: Proceedings
Publication Acceptance Date: April 22, 2004
Publication Date: July 19, 2004
Citation: Rath, N.C., Balog, J.M., Huff, G.R., Huff, W.E. 2004. Pathogenesis of avian growth plate dyschondroplasia. In: Proceedings of the International Conference on Production Diseases in Farm Animals, July 19-20, 2004, Lansing, Michigan. 2004 CDROM. Technical Abstract: Tibial dyschondroplasia (TD) is a metabolic cartilage disease characterized by the presence of an avascular plug of cartilage in the proximal tibia and tibiotarsal bones. It is a leading cause of lameness in meat-type poultry. The pathology of TD is well characterized but the etiology of the naturally occurring disease is unclear. Although genetic predisposition is considered to be a factor for the susceptibility to TD, it is more likely that exogenous factors trigger its pathogenesis. Growth plate development is a complex process rendered through a multitude of growth and metabolic interactions which culminate in endochondral bone development. Consequently, the metabolic deficiency of some key nutritional, growth, and developmental factors have been suggested to cause the pathogenesis of TD. Accordingly, these deficiencies have been thought to prevent post-proliferative chondrocytes to undergo hypertrophic maturation and subsequent bone formation. Studies in our lab have demonstrated that premature chondrocyte death is the cause for the retention of the avascular plug of cartilage which is metabolically inactive. It explains why the TD-affected tissues lack many of the growth and metabolic factors. The majority of the studies on TD are done comparing normal growth plate versus tissues in TD lesions; therefore, it is difficult to determine what initiates its pathogenesis. To address this issue we have developed an experimental model of TD by feeding one week-old broiler chicks 100 ppm thiram, a dithiocarbamate pesticide, for 24-48 h which causes severe TD lesion in more than 85% of birds. The model allows comparison of changes in the growth plate induced by thiram which may be consequential to the subsequent development of TD lesions. To determine what changes are brought about by thiram, we compared several cellular and biochemical profiles of growth plate tissues of control and treated birds using parameters of cell multiplication, gene expression associated with chondrocyte development and maturation, and cell death. Our results show that thiram does not diminish the expression of genes that would indicate impairment of chondrocyte maturation and arrest of the cells in a prehypertrophic state. Neither was there any cell multiplication that would lead to cartilage accumulation, and thickening in post-proliferative zones. However, thiram treatment caused capillary endothelial cell and chondrocyte death. Histological observation showed a gradual shrinkage in the cytoplasmic and nuclear volume of the chondrocytes which lead to their appearance resembling, prehypertrophic not hypertrophic chondrocytes. In light of our past studies which showed the chondrocytes of TD lesions failed to grow in culture and the fact that the avian growth plate is a well vascularized tissue, we surmise that thiram exerts its TD-producing effect through its ability to cause endothelial cell death by preventing the vascularity of the growth plate. The loss of blood vessels secondarily causes metabolic deficiency preventing the maturational process in prehypertrophic chondrocytes. Because several dithiocarbamate and their congeners are widely used to control insects, fungi, and rodents, it is possible that an inadvertent exposure to such chemicals during the period of intense growth may be a cause of tibial dyschondroplasia in poultry.