Regulation of growth of long bones occurs in cartilage growth plates, where proliferation of chondrocytes, matrix synthesis, and an increase in vertical height in the direction of growth all contribute to the final length of a bone. In this study, we tested the hypothesis that an increase in chondrocytic vertical height is a major variable that accounts for the decreased rate of growth of long bones in Scottish deerhound dogs that had pseudoachondroplasia. The diagnosis of pseudoachondroplasia is based, primarily, on the demonstration of alternating electron-dense and electron-lucent lamellae with a periodicity of 100 to 150 nanometers in dilated rough endoplasmic reticulum. These ultrastructural changes are similar to those seen in humans who have pseudoachondroplasia. In Scottish deerhounds that have the disease, growth of bone is approximately 65 per cent of that in normal animals. There were striking differences in the diameters of proliferating and hypertrophic chondrocytes in pseudoachondroplastic animals compared with normal animals. Specifically, the horizontal diameter of proliferating chondrocytes was 22.7 micrometers in normal animals and 11.3 micrometers in pseudoachondroplastic animals. The vertical diameter of proliferating chondrocytes was 4.8 and 7.6 micrometers in normal and pseudoachondroplastic animals. In the distal 100 micrometers of the hypertrophic zone, the mean horizontal diameter of hypertrophic chondrocytes was 29.6 and 19.1 micrometers and the mean vertical diameter was 22.8 and 18.6 micrometers in normal and pseudoachondroplastic animals. All these differences were statistically significant. The changes in vertical height resulted in a significant difference in the incremental difference in vertical height between chondrocytes from the proliferative and hypertrophic zones in normal animals (18.0 micrometers per chondrocyte) and pseudoachondroplastic animals (11.0 micrometers per chondrocyte). Each chondrocyte in the abnormal plates achieved only 61 per cent of the incremental difference of chondrocytes in normal plates. The mean cellular volume of chondrocytes in the hypertrophic zone was 13,050 cubic micrometers in the normal animals and 10,740 cubic micrometers in the pseudoachondroplastic animals. This difference was not statistically significant. These results are discussed in relation to current theories of the role of the shape and change in volume of chondrocytes in the regulation of longitudinal growth of bone. CLINICAL RELEVANCE: Abnormalities of cellular shape and orientation in the growth plates of patients who have chondrodysplasia have been well documented. However, in humans, it is not possible to make a direct comparison of the histology of the growth plate in patients who have the disease with that in age and familial-matched people who do not have the disease. The quantitative data from this canine model of pseudoachondroplasia confirm previous qualitative observations in several different chondrodysplasias in humans that there is an association between the altered shape and orientation of chondrocytes in these diseases and a decreased rate of longitudinal growth of bone. The data suggest that a biochemical defect in the disease results in an abnormality of the growth-plate matrix. This abnormality may allow a change in the shape of chondrocytes in the proliferative and hypertrophic zones of pseudoachondroplastic animals. Because the usual shape of the chondrocyte is not maintained by the matrix, the increase in cellular volume that is seen in the chondrocytes of the hypertrophic zone is not directed to longitudinal growth but, rather, allows the chondrocyte to increase in size in an indiscriminate manner.
