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.
Muscle, Smooth, Vascular
/ drug effects
Osteogenesis
/ drug effects
RANK Ligand
/ metabolism
Cell Differentiation
/ drug effects
Osteoprotegerin
/ metabolism
Myocytes, Smooth Muscle
/ drug effects
Vascular Calcification
/ pathology
Cells, Cultured
Geranyltranstransferase
/ metabolism
Core Binding Factor Alpha 1 Subunit
/ metabolism
Humans
Glycerophosphates
/ pharmacology
Osteopontin
/ metabolism
Farnesyl pyrophosphate synthase
Nitrogen-containing bisphosphonate
OPG
RANKL
Vascular calcification
Vascular smooth muscle cells
Journal
BMC cardiovascular disorders
ISSN: 1471-2261
Titre abrégé: BMC Cardiovasc Disord
Pays: England
ID NLM: 100968539
Informations de publication
Date de publication:
17 Sep 2024
17 Sep 2024
Historique:
received:
15
02
2024
accepted:
12
07
2024
medline:
18
9
2024
pubmed:
18
9
2024
entrez:
17
9
2024
Statut:
epublish
Résumé
Nitrogen-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. β-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). β-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. N-BP increases OPG expression and decreases RANKL expression via inhibition of FPPS to inhibit the osteogenic differentiation and calcification in VSMCs.
Sections du résumé
BACKGROUND
BACKGROUND
Nitrogen-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.
METHODS
METHODS
β-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).
RESULTS
RESULTS
β-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.
CONCLUSION
CONCLUSIONS
N-BP increases OPG expression and decreases RANKL expression via inhibition of FPPS to inhibit the osteogenic differentiation and calcification in VSMCs.
Identifiants
pubmed: 39289624
doi: 10.1186/s12872-024-04048-x
pii: 10.1186/s12872-024-04048-x
doi:
Substances chimiques
RANK Ligand
0
Osteoprotegerin
0
Geranyltranstransferase
EC 2.5.1.10
Core Binding Factor Alpha 1 Subunit
0
TNFRSF11B protein, human
0
TNFSF11 protein, human
0
Glycerophosphates
0
beta-glycerophosphoric acid
WWH06G87W6
Osteopontin
106441-73-0
RUNX2 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
494Subventions
Organisme : Open Research Project of Key Laboratories in Jiangsu Province Universities
ID : No.XZSYSKF2023022
Organisme : Young Talent Development Plan of Changzhou Health Commission
ID : No.CZQM2021026
Informations de copyright
© 2024. The Author(s).
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