Tibial Dyschondroplasia: A Growth Plate Abnormality Caused by Delayed Terminal Differentiation

摘要

Disruption to the orderly progression of chondrocyte maturation within the growth plate causes many physeal abnormalities resulting in abnormal bone growth. One such disorder is tibial dyschondroplasia (TD), which is a common cause of deformity and lameness in many rapidly growing animals. Cell and matrix components of the growth plate have been studied in order to determine the cause(s) of the premature arrest of chondrocyte differentiation and retention of prehypertrophic chondrocytes observed in TD. Chondrocyte proliferation proceeds normally in TD but markers of the differentiated phenotype, local growth factors and the vitamin D receptor are abnormally expressed within the prehypertrophic chondrocytes above, and within, the lesion. TD is also associated with a reduced incidence of apoptosis suggesting that the lesion contains an accumulation of immature cells that have outlived their normal life span. Immunolocalisation studies of matrix components suggest an abnormal distribution within the TD growth plate that is consistent with a failure of the chondrocytes to fully hypertrophy. In addition, the collagen matrix of the TD lesion is highly crosslinked, which may make the formed lesion more impervious to vascular invasion and osteoclastic resorption. Recent studies have applied the techniques of differential display and semi-quantitative RT-PCR to RNA obtained from discrete populations of growth plate chondrocytes of different maturational phenotype. This strategy has allowed the comparison of phenotypically identical cell fractions from normal and TD growth plates in an attempt to identify possible candidate genes for TD.