A Novel Vitamin D Receptor Agonist, VS-105, Improves Bone Mineral Density without Affecting Serum Calcium in a Postmenopausal Osteoporosis Rat Model.
A Novel Vitamin D Receptor Agonist, VS-105, Improves Bone Mineral Density without Affecting Serum Calcium in a Postmenopausal Osteoporosis Rat Model.
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DOI：
10.14218/jerp.2020.00020
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发表时间：
2020-12
期刊：
影响因子：
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通讯作者：
Atsawasuwan P
中科院分区：
文献类型：
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作者：
Wu-Wong JR;Wessale JL;Chen YW;Chen T;Oubaidin M;Atsawasuwan P
VS-105 是一种新型维生素 D 受体激动剂，其高钙血症副作用明显低于骨化三醇，是研究非高钙血症剂量的维生素 D 受体激动剂是否可以改善骨矿物质密度 (BMD) 的有用工具。在卵巢切除 (OVX) 骨质疏松大鼠模型和颅盖骨器官培养中对 VS-105 和骨化三醇进行了评估。用 VS-105（0.1、0.2 或 0.5 μg/kg，腹膜内注射，3 次/周，持续 90 天）治疗 OVX 大鼠，以剂量依赖性方式显着改善 L3 腰椎的 BMD（假手术与 OVX/载体：324 ± 14 与 279 ± 10 mg/cm2；VS-105 在0.1、0.2 和 0.5 μg/kg：分别为 306 ± 9、329 ± 12 和 327 ± 10 mg/cm2），不影响血清钙 (Ca)。 0.1 μg/kg 骨化三醇显着增加 BMD，但也增加血清 Ca。测试剂量的VS-105和骨化三醇显着抑制血清甲状旁腺激素并促进胫骨生长。对于骨重建的生物标志物，骨化三醇和VS-105均显着升高血清骨钙素。在颅盖骨器官培养中，VS-105 处理组（与骨化三醇相比）的净 Ca 释放量显着减少。 VS-105在不影响OVX大鼠血清Ca的剂量范围内有效改善BMD； VS-105 对 BMD 的改善归因于成骨细胞活性的增加和破骨细胞骨吸收的减少。
VS-105, a novel vitamin D receptor agonist with significantly less hypercalcemic side effects than calcitriol, is a useful tool to investigate whether or not a vitamin D receptor agonist at non-hypercalcemic doses could improve bone mineral density (BMD). VS-105 and calcitriol were evaluated in an ovariectomized (OVX) osteoporosis rat model and in calvariae bone organ culture. Treatment of OVX rats by VS-105 (0.1, 0.2 or 0.5 μg/kg, intraperitoneal, 3×/week, for 90 days) significantly improved BMD in the L3 lumbar vertebra in a dose-dependent manner (sham vs. OVX/vehicle: 324 ± 14 vs. 279 ± 10 mg/cm2; VS-105 at 0.1, 0.2 and 0.5 μg/kg: 306 ± 9, 329 ± 12, and 327 ± 10 mg/cm2, respectively) without affecting serum calcium (Ca). Calcitriol at 0.1 μg/kg significantly increased BMD but it also increased serum Ca. VS-105 and calcitriol at the test doses significantly suppressed serum parathyroid hormone and promoted tibia bone growth. With respect to biomarkers of bone remodeling, calcitriol and VS-105 both significantly elevated serum osteocalcin. In the calvariae bone organ culture, net Ca release was significantly less in VS-105-treated groups (vs. calcitriol). VS-105 is efficacious in improving BMD in a dose range that does not affect serum Ca in OVX rats; the improvement in BMD by VS-105 is attributable to increased osteoblastic activity and reduced osteoclastic bone resorption.