ArticleBMC cardiovascular disorders2024
Nitrogen-containing bisphosphonate induces enhancement of OPG expression and inhibition of RANKL expression via inhibition of farnesyl pyrophosphate synthase to inhibit the osteogenic differentiation and calcification in vascular smooth muscle cells.
Article in BMC cardiovascular disorders, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Geranylgeraniol as a Modulator of Mevalonate Pathway Disruption: A Scoping Review of Cellular Mechanisms and Skeletal Outcomes in Osteoporosis Models.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Cardiovascular adverse events associated with denosumab versus zoledronic acid in patients with breast cancer: a propensity score overlap weighted analysis.Breast cancer research and treatment · 2025Article
- Identification and validation of SQLE in steroid-induced osteonecrosis of the femoral head: a bioinformatics and experimental study.Journal of orthopaedic surgery and research · 2025Article
- Engineering a BMP2-risedronate complex with sustained release for osteoporosis therapy.Archives of pharmacal research · 2025Article
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Abstract
backgroundNitrogen-containing bisphosphonate(N-BP)had been found to inhibit the osteogenic differentiation and calcification in vascular smooth muscle cells (VSMCs), but the mechanism is not clear. We intend to verify that N-BP induces enhancement of OPG expression and inhibition of RANKL expression via inhibition of farnesyl pyrophosphate synthase(FPPS) to inhibit the osteogenic differentiation and calcification in VSMCs.
methodsβ-glycerophosphate (β-GP) was used to induce the osteogenic differentiation and calcification in VSMCs. VSMCs were treated with N-BP or pretreated with downstream products of farnesyl pyrophosphate synthase(FPPS) in mevalonate pathway, such as farnesol (FOH) or geranylgeraniol (GGOH). Alizarin red S staining and determination of calcium content were used to detect calcium deposition.Western Blotting were used to detect expressions of proteins(OPG and RANKL ) and osteogenic marker proteins (Runx2 and OPN).
resultsβ-GP induced the osteogenic differentiation and calcification in VSMCs, increased RANKL protein expression and had no significant effect on OPG protein expression. With the treatment of N-BP, the expression of OPG protein was increased and expression of RANKL protein was decreased in VSMCs undergoing osteogenic differentiation and calcification. In addition, N-BP reduced the osteogenic marker proteins (Runx2 and OPN) expression and calcium deposition in VSMCs undergoing osteogenic differentiation and calcification. These effects of N-BP on the osteogenic differentiation and calcification in VSMCs were concentration-dependent, which could be reversed by the downstream products of FPPS, such as FOH or GGOH.
conclusionN-BP increases OPG expression and decreases RANKL expression via inhibition of FPPS to inhibit the osteogenic differentiation and calcification in VSMCs.
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