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ARS Home » Southeast Area » Fayetteville, Arkansas » Poultry Production and Product Safety Research » Research » Publications at this Location » Publication #166988


item Rath, Narayan
item Richards, Mark
item Huff, William
item Huff, Geraldine
item Balog, Janice

Submitted to: Journal of Comparative Pathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/9/2004
Publication Date: 6/1/2005
Citation: Rath, N.C., Richards, M.P., Huff, W.E., Huff, G.R., Balog, J.M. 2005. Changes in the tibial growth plates of chickens with thiram induced dyschondroplasia. Journal of Comparative Pathology. 133:41-52.

Interpretive Summary: Some broiler chickens suffer from a leg problem tibial dyschondroplasia which makes bones fragile and leads to their lameness. We, experimentally induced the same disease by feeding 7 day-old chickens with feed, supplemented with a pesticide called thiram for two days in order to understand how this chemical may cause disease. We examined different aspects of cartilage physiology relating to cell growth and function in relation to development. Our results show that thiram kills the blood vessels in certain parts of the growing cartilage which deprives the cells of cartilage getting proper nutrition and causes their death. The cell death in the growing end of bone disrupts bone formation consequently making bone soft and easy to break or deform thereby causing leg problems.

Technical Abstract: Tibial dyschondroplasia (TD) is a metabolic cartilage disease in young poultry where endochondral bone formation is disrupted leading to the retention of a non-calcified, avascular plug of cartilage in the tibial growth plate. To elucidate the mechanisms associated with the pathogenesis of TD, we examined the changes in the growth plate of chickens that were subjected to an experimental induction of TD by the use of thiram, a fungicide. Male broiler chicks were fed diets containing 100 ppm thiram for 48 h and the changes in the growth plate was determined thereafter with respect to cell multiplication using bromodeoxyuridine (BrdU) labeling and the metabolic changes measuring alkaline phosphatase (ALP), tartarate resistant acid phosphatase (TRAP), and glutathione (GSH) concentrations. The effect on chondrocyte maturation was examined using reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of gene expression. Terminal deoxynucleotide transferase mediated 3' OH nick end labeling (TUNEL) and DNA fragmentation was used to determine the effects of thiram on cell survival. The results show that thiram-induced TD was not due to the multiplication of cells in the post proliferative zones. Thiram did not affect ALP activity that would indicate a loss of calcification potential but reduced both TRAP and the glutathione concentrations suggesting that the growth plate metabolism and remodeling functions are compromised. Thiram appeared to have no effect on the expression of type X collagen, transglutaminase, RUNX2, or matrix metalloproteinase-2 (MMP) genes suggesting that it may not alter the maturation potential of chondrocytes. On the contrary, the expressions of MMP-13 and vascular endothelial growth factor (VEGF) genes were up regulated suggesting that thiram may have some pro-angiogenic activity. However, the TUNEL assay showed that thiram induces endothelial cell apoptosis in the capillary vessels of the growth plates, as early as day 10, when TD was not visually evident. The vascular death increased on subsequent days accompanied by massive death of chondrocytes in the transition zone of growth plate. The induction of apoptosis in the growth plate was also demonstrated by DNA fragmentation. We conclude that thiram induces TD not through an increase in the multiplication of chondrocytes in the transition zone chondrocytes, nor by altering the expression of genes causing the arrest of chondrocytes in a prehypertrophic state but by creating a metabolic dysfunction which leads to the death of blood capillaries in the transition zone chondrocytes.