Previous studies have suggested that vitamin D metabolites directly influence the differentiation and maturation of chondrocytes in calcifying cartilage. Recently, this laboratory has shown that the response of chondrocyte plasma membrane and matrix vesicle enzymes to 1,25‐(OH)2D3 and 24,25‐(OH)2D3 is both cell and membrane specific. The current study demonstrates that cell replication and matrix protein synthesis are also modulated by vitamin D. Confluent, third‐passage growth zone (GC) and resting zone (RC) costochondral chondrocytes were incubated in medium containing 10−13‐10−7 M 1,25‐(OH)2D3 or 10−12‐10−6 M 24,25‐(OH)2D3. The amount of collagenase‐digestible protein (CDP) secreted into the media was inversely proportional to the concentration of fetal bovine serum (FBS). At 10% FBS, greater than 80% of the CDP was incorporated into the matrix. 1,25‐(OH)2D3 stimulated CDP and percentage collagen synthesis by GC cells but had no effect on the synthesis of noncollagenous protein (NCP). 1,25‐(OH)2D3 inhibited CDP and percentage collagen synthesis by RC cells but did not alter NCP synthesis. [3H]thymidine incorporation was inhibited in both cell types, whether confluent or subconfluent cultures were examined. At 10−6 and 10−7 M 24,25‐(OH)2D3, there was a significant decrease in CDP production and percentage collagen synthesis by RC cells but no effect on NCP. However, at 10−9 and 10−10 M hormone there was an increase in NCP production but no effect on CDP, resulting in a decrease in percentage collagen synthesis. CDP and NCP production were unaffected by 24,25‐(OH)2D3 in GC cells. High concentrations of hormone inhibited [3H]thymidine incorporation in both cell types. 24,25‐(OH)2D3 also stimulated [3H]uridine incorporation at 10−8 and 10−9 M in RC cells. These data support the hypothesis that vitamin D metabolites influence the development and maturation of calcifying cartilage and that the response of cells to hormone is dependent on their state of differentiation.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Orthopedics and Sports Medicine