{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T15:55:16Z","timestamp":1772985316947,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"vor","delay-in-days":314,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100011841","name":"Xinxiang Medical University","doi-asserted-by":"publisher","award":["KFKTZD202106"],"award-info":[{"award-number":["KFKTZD202106"]}],"id":[{"id":"10.13039\/501100011841","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Stem Cells International"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Osteogenic differentiation is a crucial process in which bone marrow mesenchymal stem cells (BMSCs) differentiate into osteoblasts, involving the regulation of multiple genes and signaling pathways. The\n                      <jats:italic>TSC22D3<\/jats:italic>\n                      gene plays an important role in various biological processes (BPs), but its specific function in osteogenic differentiation remains unclear. This study aims to explore the regulatory role of the\n                      <jats:italic>TSC22D3<\/jats:italic>\n                      gene in osteogenic differentiation and its molecular mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      By analyzing microarray datasets (GSE12266, GSE18043, and GSE80614), the limma package was used to screen for differentially expressed genes (DEGs). Combined with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, key genes and signaling pathways related to osteogenic differentiation were identified. Further, through protein\u2013protein interaction (PPI) network analysis and the Finding Regulatory Elements by Differential Expression and Network\u2010Based Statistical Analysis (FRIEND) method,\n                      <jats:italic>TSC22D3<\/jats:italic>\n                      was screened out as a core hub gene. For experimental validation, the bioinformatics analysis results were intersected with the transcriptome sequencing data from our research group to further confirm the core molecules. Lentivirus\u2010mediated interference technology was used to downregulate and overexpress\n                      <jats:italic>TSC22D3<\/jats:italic>\n                      expression, and the impact of\n                      <jats:italic>TSC22D3<\/jats:italic>\n                      on osteogenic differentiation was assessed through RT\u2010qPCR, Western blotting, alkaline phosphatase (ALP) staining, phalloidin staining, and calcium deposition assays.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>TSC22D3<\/jats:italic>\n                      is significantly upregulated during osteogenic differentiation; its downregulation can lead to reduced expression of osteogenic differentiation marker genes (such as runt\u2010related transcription factor 2 [Runx2], osterix [OSX], osteocalcin [OCN], and osteopontin [OPN]), as well as a significant decrease in ALP activity and calcium deposition. GO and KEGG analyses indicate that\n                      <jats:italic>TSC22D3<\/jats:italic>\n                      is closely associated with pathways including the cell cycle, cytoskeleton, and WNT signaling. Furthermore, Gene Set Enrichment Analysis (GSEA) analysis has further revealed the potential regulatory mechanism of\n                      <jats:italic>TSC22D3<\/jats:italic>\n                      in osteogenic differentiation. Rescue experiments have confirmed that\n                      <jats:italic>TSC22D3<\/jats:italic>\n                      can promote the osteogenic differentiation of BMSCs and induce the rearrangement of cytoskeletal structure.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study reveals that\n                      <jats:italic>TSC22D3<\/jats:italic>\n                      is essential for osteogenic differentiation. Its upregulation promotes osteogenic marker expression, ALP activity, and calcium deposition, while its downregulation inhibits these processes.\n                      <jats:italic>TSC22D3<\/jats:italic>\n                      affects cytoskeletal rearrangement during osteogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/sci\/1047964","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T10:31:46Z","timestamp":1762857106000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification and Validation of a New Functional Gene\n                    <i>TSC22D3<\/i>\n                    for hBMSCs 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