Effect of interleukin‐1β on bone morphogenetic protein‐9‐induced osteoblastic differentiation of human periodontal ligament fibroblasts

Bone morphogenetic protein‐9 (BMP‐9) has been shown to potently induce osteoblastic differentiation of periodontal ligament fibroblasts (PDLFs) and may be a candidate therapeutic agent for periodontal tissue healing/regeneration, but the effect of the inflammatory environment of periodontitis on suc...

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Veröffentlicht in:European journal of oral sciences 2021-08, Vol.129 (4), p.e12792-n/a
Hauptverfasser: Ebe, Yukari, Nakamura, Toshiaki, Hasegawa‐Nakamura, Kozue, Noguchi, Kazuyuki
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Sprache:eng
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Zusammenfassung:Bone morphogenetic protein‐9 (BMP‐9) has been shown to potently induce osteoblastic differentiation of periodontal ligament fibroblasts (PDLFs) and may be a candidate therapeutic agent for periodontal tissue healing/regeneration, but the effect of the inflammatory environment of periodontitis on such approaches is unclear. We investigated whether interleukin‐1β (IL‐1β) affected BMP‐9‐mediated osteoblastic differentiation of human (h) PDLFs. IL‐1β suppressed BMP‐9‐induced osteogenic differentiation of hPDLFs, as evidenced by reduced alkaline phosphatase (ALP) activity and mineralization, and the downregulated expression of BMP‐9‐mediated bone‐related genes, RUNX2, SP7, IBSP, and SPP1. In hPDLFs, with or without BMP‐9, IL‐1β increased the protein expression of activin A, a BMP‐9 antagonist, and decreased follistatin protein, an antagonist of activin A. Similarly, IL‐1β upregulated the expression of the activin A gene and downregulated that of the follistatin gene. Notably, follistatin re‐established BMP‐9‐induced ALP activity suppressed by IL‐1β. Activin A inhibited the expression of BMP‐9‐responsive genes and BMP‐9‐induced ALP activity, while follistatin re‐established them. Finally, extracellular signal‐regulated kinase 1/2 (ERK1/2), p38, and nuclear factor‐kappa B (NF‐κB) inhibition significantly blocked IL‐1β‐induced activin A gene expression. Our data indicate that IL‐1β inhibits BMP‐9‐induced osteoblastic differentiation of hPDLFs, possibly by promoting activin A production via the ERK1/2, p38, and NF‐κB pathways.
ISSN:0909-8836
1600-0722
DOI:10.1111/eos.12792