Silencing P2Y₁₂ and P2Y₁₃ receptors rehabilitates the ADP-induced P2Y₁-mediated osteogenic commitment of post-menopausal mesenchymal stromal cells

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background Participation of ADP-sensitive metabotropic P2Y 1 , P2Y 12 and P2Y 13 receptors in human osteogenesis is controversial. Here, we investigated the variations in the expression and bone-forming properties of the P2Y 1 R in osteogenic-differentiating bone marrow-derived mesenchymal stromal cells (BM-MSCs) isolated from post-menopausal (Pm) women. We also tested whether observed P2Y 1 -related functional deficits result from the crosstalk with co-localized P2Y 12 and P2Y 13 receptors. Methods Pm BM-MSCs were cultured in an osteogenic-inducing medium in either the absence or presence of the selective P2Y 1 receptor agonist, MR2365; this compound was applied alone or after cells' incubation with selective P2Y 12 and P2Y 13 receptor antagonists or short hairpin RNAs designed to silence P2Y 12 or P2Y 13 receptors gene expression. Results BM-MSCs present immunoreactivity against all ADP-sensitive P2Y receptor subtypes, but their relative density varied among different Pm women and with the time of the cells in the culture. The P2Y 1 receptor agonist increased the alkaline phosphatase activity and bone nodule formation in BM-MSCs originating from a younger female, but it failed to promote the osteogenic differentiation of BM-MSCs from Pm women unless P2Y 12 or P2Y 13 receptors are blocked with AR-C66096 and MRS211, respectively. Silencing the P2Y 13 , but not the P2Y 12 , rece

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

Browse all related research

Filter the research library by this study's title keywords, author, or publication year.