Relative potencies of 1,25-(OH)2D3 and 19-Nor-1,25-(OH)2D2 on inducing differentiation and markers of bone formation in MG-63 cells

• Published in: Journal of the American Society of Nephrology Vol. 12; no. 7; pp. 1468 - 1474
• Main Authors: FINCH, Jane L, DUSSO, Adriana S, PAVLOPOULOS, Tricia, SLATOPOLSKY, Eduardo A
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.07.2001
• Subjects: Biological and medical sciences; Hormones. Endocrine system; Medical sciences; Pharmacology. Drug treatments; Endocrinopathy; Human; Cell culture; Secondary; Biological marker; In vivo; Chemotherapy; Regulation(control); Treatment; Vitamin D; Parathyroid diseases; Analog; Established cell line; Osteoblast; Differentiation; Hyperparathyroidism; Biological receptor
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/ASN.V1271468

19-Nor-1,25-(OH) 2 D 2 , an analog of 1,25-(OH) 2 D 3 , 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) 2 D 2 is approximately 10 times less active than 1,25-(OH) 2 D 3 in 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) 2 D 2 also could be less potent than 1,25-(OH) 2 D 3 on 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) 2 D 3 and 19-nor-1,25-(OH) 2 D 2 had 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) 2 D 3 and 19-nor-1,25-(OH) 2 D 2 induction 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) 2 D 3 —induced ALP activity in this cell line. Transforming growth factor-β alone had no effect, whereas 1,25-(OH) 2 D 3 and 19-nor-1,25-(OH) 2 D 2 increased ALP activity similarly. These studies demonstrate that 19-nor-1,25-(OH) 2 D 2 has the same potency as 1,25-(OH) 2 D 3 not 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) 2 D 2 would have deleterious effects on bone remodeling.