ArticleJournal of orthopaedic surgery and research2024
The SPI1/SMAD5 cascade in the promoting effect of icariin on osteogenic differentiation of MC3T3-E1 cells: a mechanism study.
Article in Journal of orthopaedic surgery and research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.
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Who cites it
5 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Efficacy and safety of Epimedium total flavonoids for primary osteoporosis: a systematic review and meta-analysis.Frontiers in pharmacology · 2024Pooled it
- Research progress on the intervention of osteoporosis by Chinese herbal monomers based on the Nrf2/NF-κB/MAPK pathway.Frontiers in endocrinology · 2026Review
- MiR-328-5p/BCL7A axis is involved in fracture healing by modulating osteoblast function.Journal of orthopaedic surgery and research · 2025Article
- Transcription factor SMAD5 upregulates ALG5 to alleviate osteoporosis development by inducing osteogenic differentiation.Journal of orthopaedics · 2025Article
- Icariin against osteoporosis: a review of advances in molecular mechanisms to biomedical applications.Frontiers in pharmacology · 2025Review
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Authors and funding
3 authors.
Funding
Abstract
backgroundDysregulation of osteogenic differentiation is a crucial event during osteoporosis. The bioactive phytochemical icariin has become an anti-osteoporosis candidate. Here, we elucidated the mechanisms underlying the promoting function of icariin in osteogenic differentiation.
methodsMurine pre-osteoblast MC3T3-E1 cells were stimulated with dexamethasone (DEX) to induce osteogenic differentiation, which was evaluated by an Alizarin Red staining assay and ALP activity measurement. The mRNA amounts of SPI1 and SMAD5 were detected by real-time quantitative PCR. Expression analysis of proteins, including osteogenic markers (OPN, OCN and RUNX2) and autophagy-associated proteins (LC3, Beclin-1, and ATG5), was performed by immunoblotting. The binding of SPI1 and the SMAD5 promoter was predicted by the Jaspar
resultsDuring osteogenic differentiation of MC3T3-E1 cells, SPI1 and SMAD5 were upregulated. Functionally, SPI1 overexpression enhanced autophagy and osteogenic differentiation of MC3T3-E1 cells, while SMAD5 downregulation exhibited opposite effects. Mechanistically, SPI1 could enhance SMAD5 transcription and expression. Downregulation of SMAD5 also reversed SPI1 overexpression-induced autophagy and osteogenic differentiation in MC3T3-E1 cells. In MC3T3-E1 cells under DEX stimulation, icariin increased SMAD5 expression by upregulating SPI1. Furthermore, icariin could attenuate SPI1 depletion-imposed inhibition of autophagy and osteogenic differentiation of MC3T3-E1 cells.
conclusionOur findings demonstrate that the SPI1/SMAD5 cascade, with the ability to enhance osteogenic differentiation, underlies the promoting effect of icariin on osteogenic differentiation of MC3T3-E1 cells.
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