骨芽細胞分化を標的とした新規経口骨粗鬆症治療薬の開発

書誌事項

タイトル別名
  • A Novel Oral Anti-osteoporosis Drug with Osteogenesis-promoting Effects <i>via</i> Osteoblast Differentiation
  • Symposium Review 骨芽細胞分化を標的とした新規経口骨粗鬆症治療薬の開発
  • Symposium Review コツガ サイボウ ブンカ オ ヒョウテキ ト シタ シンキ ケイコウ コツソショウショウ チリョウヤク ノ カイハツ

この論文をさがす

抄録

<p>Osteoporosis increases the risk of bone fractures (e.g., the femur), reduces a person's activities of daily living (ADL) and increases the likelihood of being bedridden. Therapeutic drugs for osteoporosis include oral bisphosphonates and intravenous receptor activator of nuclear factor-κB ligand (RANKL) antibodies, both of which suppress osteoclast activity, as well as the subcutaneously administered recombinant human parathyroid hormone (PTH), which activates osteoblasts. However, there is currently no oral osteogenesis-promoting drug. In the present study, we found a low-molecular-weight compound, KY-273, with osteogenesis promoting effects. KY-273 induced osteoblast differentiation in ST2 cells and in rat bone marrow-derived mesenchymal stem cells at a dose of 0.1 μM. On the other hand, KY-273 did not clearly exert differentiation effects in osteoclasts, chondrocytes, adipocytes, or myoblasts. In ovariectomized rats, KY-273 clearly increased serum bone alkaline phosphatase (ALP) by at a dose of 3 mg/kg for 8 weeks, and increased both the cortical bone volume and medullary volume of the diaphyseal and epiphyseal regions of femoral bone, but did not affect trabecular bone. Although alendronate (used to decrease bone loss) increased trabecular bone, it did not have any significant effects on cortical bone. PTH increased epiphysis cortical and trabecular bone volume, and reduced medullary volume. KY-273 also displayed good oral absorption in rats. In conclusion, KY-273 is a promising candidate for use as an oral anti-osteoporosis drug with osteogenesis promoting effects.</p>

収録刊行物

  • 薬学雑誌

    薬学雑誌 139 (1), 19-25, 2019-01-01

    公益社団法人 日本薬学会

被引用文献 (2)*注記

もっと見る

参考文献 (13)*注記

もっと見る

詳細情報 詳細情報について

問題の指摘

ページトップへ