{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T08:31:22Z","timestamp":1775032282331,"version":"3.50.1"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioeng. Biotechnol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Mesenchymal stem cell (MSC) dysfunction contributes to impaired bone regeneration in osteoporosis. Lamin B1, a nuclear lamina protein implicated in stem cell aging, has an unclear role in osteogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We examined Lamin B1 expression during osteogenic differentiation, assessed its pathological alterations in OVX-derived BMSCs, and generated Lamin B1\u2013knockout MSCs to evaluate effects on osteogenesis, migration, and KAT2A regulation. We performed transcriptomic profiling and intra\u2013bone marrow transplantation in OVX mice to determine functional relevance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Lamin B1 expression progressively decreased during osteogenic induction but was markedly upregulated in OVX BMSCs, where it correlated with impaired migration. Lamin B1 deletion enhanced alkaline phosphatase activity, mineralization, and migration. Mechanistically, Lamin B1 interacted with KAT2A and promoted its ubiquitin-dependent degradation, thereby reducing KAT2A protein stability. Knockdown-induced transcriptional changes indicated activation of osteogenic and migration-related pathways.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , Lamin B1-deficient MSCs showed improved engraftment and substantially enhanced bone regeneration, reflected by increased BMD, BV\/TV, MAR, and BFR in OVX mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Lamin B1 depletion enhances BMSC osteogenesis by preventing KAT2A degradation. Lamin B1-deficient BMSCs provide a promising gene-enhanced cell therapy strategy for osteoporosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fbioe.2026.1803514","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T05:40:25Z","timestamp":1775022025000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetically reprogrammed BMSCs with Lamin B1 depletion enhance bone regeneration for osteoporosis therapy"],"prefix":"10.3389","volume":"14","author":[{"given":"Xuekun","family":"Fu","sequence":"first","affiliation":[{"name":"Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine","place":["Shenzhen, China"]},{"name":"Department of Systems Biology, School of Life Sciences, Southern University of Science and Technology","place":["Shenzhen, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaochuan","family":"Huo","sequence":"additional","affiliation":[{"name":"Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine","place":["Shenzhen, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunhao","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, School of Life Sciences, Southern University of Science and Technology","place":["Shenzhen, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanson","family":"Hsu","sequence":"additional","affiliation":[{"name":"Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California, San Diego","place":["La Jolla, CA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, School of Life Sciences, Southern University of Science and Technology","place":["Shenzhen, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhe","family":"Lei","sequence":"additional","affiliation":[{"name":"Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine","place":["Shenzhen, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Peking University Shenzhen Hospital","place":["Shenzhen, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Liu","sequence":"additional","affiliation":[{"name":"Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine","place":["Shenzhen, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jincheng","family":"Zeng","sequence":"additional","affiliation":[{"name":"Dongguan Key Laboratory of Medical Bioactive Molecular Developmental and Translational Research, Guangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, Guangdong Medical University","place":["Dongguan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Songqing","family":"Lin","sequence":"additional","affiliation":[{"name":"Shenzhen Futian District Maternal and Child Health Hospital","place":["Shenzhen, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, School of Life Sciences, Southern University of Science and Technology","place":["Shenzhen, China"]},{"name":"Institute of Integrated Bioinfomedicine and Translational Science (IBTS), School of Chinese Medicine, Hong Kong Baptist University","place":["Hong Kong SAR, China"]},{"name":"State Key Laboratory of Proteomics, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1359\/jbmr.081010","article-title":"Effect of lamin A\/C knockdown on osteoblast differentiation and function","volume":"24","author":"Akter","year":"2009","journal-title":"J. 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