Differential Effects of lα,25-Dihydroxycholecalciferol and 24R,25-Dihydroxycholecalciferol on the Proliferation and the Differentiated Phenotype of Rabbit Costal Chondrocytes in Culture*

Abstract

Lα,25-Dihydroxycholecalciferol [1,25-(OH)₂D₃] stimulated the proliferation and DNA synthesis of rabbit costal growth cartilage cells in the logarithmic growth phase in culture. The stimulatory effects of 1,25-(OH)₂D₃ were observable at a concentration of 10^-10 M and maximal at a concentration of 10-8 M. On the other hand, 1,25-(OH)₂D₃ inhibited their expression of the cartilage phenotype, as judged morphologically, histochemically, and biochemically by a decrease in glycosaminoglycan (GAG) synthesis. The inhibition of GAG synthesis was also dose dependent and observable at a concentration of 10^-10 M. 1,25-(OH)₂D₃ also stimulated the proliferation of resting cartilage cells and inhibited their GAG synthesis, but its effects on these cells were less than those on growth cartilage cells, suggesting that 1,25-(OH)₂D₃ acts more specifically on growth cartilage cells than on resting cartilage cells. 1,25-(OH)₂D₃ had no effect on either DNA synthesis or GAG synthesis of growth cartilage cells in confluent cultures. 24R,25-Dihydroxycholecalciferol [24,25-(OH)₂D₃] had no effect on proliferation, DNA synthesis, or GAG synthesis of growth cartilage cells in the logarithmic growth phase. However, 24,25-(OH)₂D₃ had no effect on DNA synthesis of these cells in confluent cultures, but stimulated their expression of the cartilage phenotype. The stimulatory effect was dose dependent and maximal at 10^-7 M. Since chondrocytes express their differentiated phenotype as they become confluent in culture, these results suggest that 1,25-(OH)₂D₃ stimulates the growth of rapidly proliferating chondrocytes with a poorly differentiated phenotype and suppresses their expression of the cartilage phenotype, while 24,25-(OH)₂D₃ stimulates expression of the differentiated phenotype of highly differentiated chondrocytes. (Endocrinology122: 831–839, 1988)