Gene expression and tibial dyschondroplasia

Tibial dyschondroplasia (TD) is a skeletal deformity associated with rapid growth in a number of avian species. The disease is the result of a disrupt ion in the cascade of events that occur in the epiphyseal growth plate. Whe reas the incidence of TD is susceptible to genetic selection, no specific g enetic defect has been identified. Although there are extensive data descri bing the morphological and biochemical characteristics of the lesion, the m echanism of lesion formation is unknown. However, naturally occurring or in duced genetic mutations in other species can provide important clues to pos sible mechanisms responsible for lesion development. Disruption of normal c hondrocyte differentiation by constitutive activation of the parathyroid ho rmone/parathyroid hormone-related peptide (PTH/PTHrP) receptor, inactivatio n of the fibroblast growth factor receptor-3 (FGFR-3) receptor, and blockin g vascular endothelial growth factor (VEGF) signaling all result in lesions that resemble TD. Impairment of vascular penetration due to the ablation o f matrix metalloproteinase-9 (MMP-9) or tartrate-resistant acid phosphatase (TRAP) activity also results in similar cartilage abnormalities. We have i ntegrated these observations with our current knowledge of TD to describe a hypothesis for the sequence of events responsible for the development of t ibial dyschondroplastic lesions.