{Reference Type}: Journal Article
{Title}: Ataluren prevented bone loss induced by ovariectomy and aging in mice through the BMP-SMAD signaling pathway.
{Author}: Zeng L;Gu R;Li W;Shao Y;Zhu Y;Xie Z;Liu H;Zhou Y;
{Journal}: Biomed Pharmacother
{Volume}: 166
{Issue}: 0
{Year}: 2023 Oct 17
{Factor}: 7.419
{DOI}: 10.1016/j.biopha.2023.115332
{Abstract}: Both estrogen deficiency and aging may lead to osteoporosis. Developing novel drugs for treating osteoporosis is a popular research direction. We screened several potential therapeutic agents through a new deep learning-based efficacy prediction system (DLEPS) using transcriptional profiles for osteoporosis. DLEPS screening led to a potential novel drug examinee, ataluren, for treating osteoporosis. Ataluren significantly reversed bone loss in ovariectomized mice. Next, ataluren significantly increased human bone marrow-derived mesenchymal stem cell (hBMMSC) osteogenic differentiation without cytotoxicity, indicated by the high expression index of osteogenic differentiation genes (OCN , BGLAP, ALP, COL1A, BMP2, RUNX2). Mechanistically, ataluren exerted its function through the BMP-SMAD pathway. Furthermore, it activated SMAD phosphorylation but osteogenic differentiation was attenuated by BMP2-SMAD inhibitors or small interfering RNA of BMP2. Finally, ataluren significantly reversed bone loss in aged mice. In summary, our findings suggest that the DLEPS-screened ataluren may be a therapeutic agent against osteoporosis by aiding hBMMSC osteogenic differentiation.