Genetically reprogrammed BMSCs with Lamin B1 depletion enhance bone regeneration for osteoporosis therapy

Background: 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. Methods: We examined Lamin B1 expression during osteogenic differentiation, assessed its pathological alterations in OVX-derived BMSCs, and generated Lamin B1-knockout MSCs to evaluate effects on osteogenesis, migration, and KAT2A regulation. We performed transcriptomic profiling and intra-bone marrow transplantation in OVX mice to determine functional relevance. Results: , Lamin B1-deficient MSCs showed improved engraftment and substantially enhanced bone regeneration, reflected by increased BMD, BV/TV, MAR, and BFR in OVX mice. Conclusion: Lamin B1 depletion enhances BMSC osteogenesis by preventing KAT2A degradation. Lamin B1-deficient BMSCs provide a promising gene-enhanced cell therapy strategy for osteoporosis.