Regulation of CYP27B1 mRNA Expression in Primary Human Osteoblasts

The enzyme 1 alpha-hydroxylase (gene CYP27B1) catalyzes the synthesis of 1,25(OH)(2)D in both renal and bone cells. While renal 1 alpha-hydroxylase is tightly regulated by hormones and 1,25(OH)(2)D itself, the regulation of 1 alpha-hydroxylase in bone cells is poorly understood. The aim of this study was to investigate in a primary human osteoblast culture whether parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), calcitonin, calcium, phosphate, or MEPE affect mRNA levels of CYP27B1. Our results show that primary human osteoblasts in the presence of high calcium concentrations increase their CYP27B1 mRNA levels by 1.3-fold. CYP27B1 mRNA levels were not affected by PTH1-34, rhFGF23, calcitonin, phosphate, and rhMEPE. Our results suggest that the regulation of bone 1 alpha-hydroxylase is different from renal 1 alpha-hydroxylase. High calcium concentrations in bone may result in an increased local synthesis of 1,25(OH)(2)D leading to an enhanced matrix mineralization. In this way, the local synthesis of 1,25(OH)(2)D may contribute to the stimulatory effect of calcium on matrix mineralization.