Frontiers in bioengineering and biotechnology · 2026
Genetically reprogrammed BMSCs with Lamin B1 depletion enhance bone regeneration for osteoporosis therapy.
СтатьяНазвание и аннотация: Перевод в очереди
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Fu Xuekun, Huo Shaochuan, Cao Chunhao, Hsu Hanson, Huang Jie, Lei Yuhe, Li Jie, Liu Peng, Zeng Jincheng, Lin Songqing, Liang Chao
Аннотация
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 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. In vivo, 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.
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 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. In vivo, 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.