ArticlePloS one2023
BushenHuoxue formula promotes osteogenic differentiation via affecting Hedgehog signaling pathway in bone marrow stem cells to improve osteoporosis symptoms.
Article in PloS one, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
4 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.
- Mechanisms and traditional Chinese medicine therapeutics for primary osteoporosis: an integrated perspective.Frontiers in endocrinology · 2025Pooled it
- Recent advances in the multifaceted mechanisms of catalpol in treating osteoporosis.Frontiers in pharmacology · 2025Review
- LINC01133 promotes the osteogenic differentiation of bone marrow mesenchymal stem cells by upregulating CTNNB1 by acting as a sponge for miR-214-3p.Journal of orthopaedic surgery and research · 2024Article
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6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe BushenHuoxue formula (BSHX) has been previously demonstrated to ameliorate osteoporosis, but the mechanisms underlying this phenomenon are currently unclear. The present study aims at investigating the mechanisms that BSHX induces osteogenesis.
methodsWe established an osteoporosis model in rats by bilateral ovariectomy and then treated the rats with an osteogenic inducer (dexamethasone, β-sodium glycerophosphate and Vitamin C) and BSHX. After that, bone marrow density and histopathological bone examination were evaluated by using HE staining and immunohistochemistry, respectively. We also assessed the differentiation of bone marrow mesenchymal stem cells (BMSCs) into osteoblasts by using immunofluorescence staining. ALP, BMP, and COL1A1 levels were determined by ELISA. We identified genes involved in pathogenesis of osteoporosis through Gene Expression Omnibus (GEO) database and subsequently selected Hedgehog signaling-related genes Shh, Ihh, Gli2, and Runx2 for assessment via qRT-PCR and ELISA, Western blotting. Network pharmacology analysis was performed to identify bioactive metabolites of BSHX.
resultsBSHX treatment in osteoporosis model rats promoted tightening of the morphological structure of the trabecular bone and increased the bone mineral density (BMD). BSHX also increased levels of osteoblast makers ALP, BMP, and COL1A1. Additionally, bioinformatics analysis of the GEO dataset showed that Hedgehog signaling pathway was involved in pathogenesis of osteoporosis, especially related genes Shh, Ihh, Gli2, and Runx2. Remarkably, BHSX upregulated these genes indispensably involved in the osteogenesis-related Hedgehog signaling pathway in both bone tissue and BMSCs. Importantly, we identified that quercetin was the active compounds that involved in the mechanism of BSHX-improved OP via affecting Hedgehog-related genes.
conclusionOur results indicate that BSHX promotes osteogenesis by improving BMSC differentiation into osteoblasts via increased expression of Hedgehog signaling-related genes Shh, Ihh, Gli2, and Runx2, and quercetin was the bioactive compound of BSHX.
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