Abstract. 19-Nor-1,25-(OH)2D2, an analog of 1,25-(OH)2D3, is used to treat secondary hyperparathyroidism because it suppresses parathyroid hormone synthesis and secretion with lower calcemic and phosphatemic activities. 19-Nor-1,25-(OH)2D2is approximately 10 times less active than 1,25-(OH)2D3in promoting bone resorption, which accounts in part for the low potency of this analog in increasing serum calcium and phosphorus. Concern that 19-nor-1,25-(OH)2D2also could be less potent than 1,25-(OH)2D3on bone formation led to a comparison of the potency of both compounds on osteoblasts. In the human osteoblast-like cell line MG-63, 1,25-(OH)2D3and 19-nor-1,25-(OH)2D2had a similar potency in upregulating vitamin D receptor content and suppressing proliferation. Both sterols caused a similar reduction in DNA content and proliferating cell nuclear antigen protein expression. Time-course and dose-response studies on 1,25-(OH)2D3and 19-nor-1,25-(OH)2D2induction of the marker of bone formation, osteocalcin, showed overlapping curves. The effects on alkaline phosphatase (ALP) activity also were studied in MG-63 cells that had been co-treated with either sterol and transforming growth factor-β, an enhancer of 1,25-(OH)2D3—induced ALP activity in this cell line. Transforming growth factor-β alone had no effect, whereas 1,25-(OH)2D3and 19-nor-1,25-(OH)2D2increased ALP activity similarly. These studies demonstrate that 19-nor-1,25-(OH)2D2has the same potency as 1,25-(OH)2D3not only in inducing vitamin D receptor content, osteocalcin levels, and ALP activity but also in controlling osteoblastic growth. Therefore, it is unlikely that 19-nor-1,25-(OH)2D2would have deleterious effects on bone remodeling.
Serine Protease HTRA1 Antagonizes Transforming Growth Factor-β Signaling by Cleaving Its Receptors and Loss of HTRA1 In Vivo Enhances Bone Formation