The role of amino bisphosphonates zoledronate and alendronate in shaping immunomodulatory profile and angiogenic potential of human periodontal ligament stem 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)

Bisphosphonate-related osteonecrosis of the jaw is a significant complication arising from the use of nitrogen-containing bisphosphonates such as Zoledronate (ZOL) and Alendronate (ALN). Although the effects of amino bisphosphonates on bone cells are well established, their influence on human periodontal ligament stem cells (hPDLSCs) remains inadequately explored. This study aimed to evaluate the influence of clinically relevant doses of ZOL and ALN on hPDLSCs secretome composition and its involvement in vascular changes reported in BRONJ. hPDLSCs isolated from the impacted third molar were exposed to increasing concentrations of ZOL (1 μM, 1.5 μM, 2 μM) or ALN (2 μM, 5 μM, 10 μM) for five days. Cytokine assay was directed to measure the levels of IL-1α, IL-6, IL-8, VEGF, and MCP-1. PD-L1 quantification was conducted by immunofluorescence, western blotting and flow cytometry. The angiogenic potential of hPDLSCs-derived secretome after preconditioning with ZOL or ALN was assessed on endothelial cells proliferation, migration, and tube-forming ability. Both ZOL and ALN treatment of hPDLSCs did not result in any significant changes in the secretion of inflammatory markers (IL-1α, IL-6, IL-8, VEGF and MCP-1). ZOL 1.5 μM (p < 0.0001) and 2 μM (p < 0.05) induced a down-regulation of total PD-L1. ALN 2 μM and 5 μM promoted a reduction of total (p < 0.0001) and surface (p < 0.01) PD-L1

Evidence level

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

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