Quantitative three-dimensional analysis of chondrocytic kinetic responses to short-term stapling of the rat proximal tibial growth plate

Although it has been demonstrated clinically that controlled compression ac ross a growth plate will slow the rate of endochondral ossification and thu s can be used to correct angular limb deformities, the cellular-based mecha nism by which altered growth is achieved is poorly understood. This study u sed short-term uniaxial stapling of the rat proximal tibial growth plate as an experimental system to study chondrocytic responses in the growth plate that account quantitatively for the decreased rate of growth. Growth plate s were labeled with oxytetracycline to measure bone growth, and with bromod eoxyuridine to analyze proliferative cell kinetics. Multiple indicators of chondrocytic activity, measured by stereological parameters, were analyzed using growth rate as the primary dependent variable. The unique feature of this analysis was the creation of three-dimensional reconstructions that al lowed analysis of data in all directions with distance from the staple. A s ignificant observation was that for the entire operated limb after both 3 a nd 6 days, all chondrocytic kinetic parameters were affected, indicating th at proliferative and hypertrophic responses both act to decrease growth rat e in response to stapling. This contradicted our hypothesis that proliferat ive and hypertrophic responses could occur independently, and that small ch anges in rate would be attributed primarily to the former and large changes to the latter. The data from this study also demonstrate that volume regul ation during hypertrophy can be affected by a primarily mechanical perturba tion. Because changes in hypertrophic cell number and volume throughout the growth plate that occur by day 3 remain similar at day 6, the initial modu lation of chondrocytic volume and shape may represent the limit of the resp onse while maintaining a growth plate capable of continued growth. Copyrigh t (C) 2000 S. Karger AG. Basel.