Monoclonal Antibody Enhanced Stimulation of Human Growth Hormone Action In Vitro Using Ovine Costal Cartilage Growth Plate Chondrocytes

Investigations into the mechanism underlying antibody-mediated enhancement of growth hormone action have been hampered by the lack of an in vitro assay system. In this work, we have used isolated ovine costal cartilage growth plate chondrocytes to demonstrate, for the first time, that monoclonal antibody EB1 can enhance the proliferative actions of human growth hormone on this cell type. Chondrocytes were cultured for 14 days prior to exposure to GH+/-monoclonal antibody EB1 for a 4-day treatment period. Human growth hormone alone promoted a significant dose-dependent increase in chondrocyte proliferation; maximal stimulation was achieved at about 3.3-10 ng/ml growth hormone, and at higher doses of growth hormone, the response declined. Monoclonal antibody EB1 was shown to enhance the proliferative activity of 10 ng/ml human growth hormone in a significant dose dependent fashion. In conclusion, our results demonstrate that an antibody capable of enhancing GH activity in vivo also has the capacity to potentiate GH activity in vitro. This system may provide an important tool for investigations into the mechanism of GH action, and how this is modified by GH enhancing MAbs.