{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T01:17:03Z","timestamp":1788225423610,"version":"build-2803163510"},"reference-count":37,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Osteoporosis (OP) is characterized by low bone mass and impaired bone microarchitecture, and the long-term use of current therapies is limited by adverse effects and poor adherence. This study sought to identify drugs that could be repurposed for glucocorticoid-induced osteoporosis. Methods: Single-cell RNA-sequencing data from two subjects with osteoporotic fractures and three control subjects were analyzed to identify transcriptional changes in osteoblasts. Candidate drugs were screened using ASGARD and L1000 drug-response signatures. Two-sample Mendelian randomization was used to examine associations between genetically predicted expression of drug-target genes and osteoporosis risk. Quinidine was tested in dexamethasone-treated Tu and Tg(Ola.Sp7:nlsGFP) zebrafish larvae using Alizarin Red staining, fluorescence imaging, and qRT-PCR. Adult zebrafish were assessed by micro-CT. Results: Four candidate drugs were identified, of which quinidine was selected for experimental evaluation. Genetically predicted SCN5A expression was positively associated with osteoporosis risk. Quinidine partially restored cranial mineralization in dexamethasone-treated larvae, with the greatest effect at 10 \u03bcmol\/L; the 100 \u03bcmol\/L treatment was less effective. Quinidine also altered the expression of several bone-remodeling-related genes. In adult zebrafish, quinidine treatment was associated with higher bone mineral density and bone volume fraction than dexamethasone treatment alone. Conclusions: Quinidine alleviated several dexamethasone-induced skeletal phenotypes in zebrafish and represents a candidate for further drug-repurposing studies in osteoporosis. Direct validation of its molecular mechanism and safety profile is still required.<\/jats:p>","DOI":"10.3390\/genes17091060","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T01:05:26Z","timestamp":1788224726000},"page":"1060","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Drug Repositioning Based on Single-Cell Transcriptomics Data Identifies Quinidine as a Potential Drug for Treating Osteoporosis"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1808-8870","authenticated-orcid":false,"given":"Rong","family":"Wang","sequence":"first","affiliation":[{"name":"Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Jia-Li","family":"Li","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Kun","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Xuan","family":"Lu","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"}]},{"given":"Qian-Qian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Qin","family":"Zeng","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Yun","family":"Deng","sequence":"additional","affiliation":[{"name":"Zebrafish Genetics Laboratory, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3181-3704","authenticated-orcid":false,"given":"Xiao-Chao","family":"Qu","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Xiang-Ding","family":"Chen","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Li-Jun","family":"Tan","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Noh, J.Y., Yang, Y., and Jung, H. 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