Premium
Effect of interleukin‐1β on bone morphogenetic protein‐9‐induced osteoblastic differentiation of human periodontal ligament fibroblasts
Author(s) -
Ebe Yukari,
Nakamura Toshiaki,
HasegawaNakamura Kozue,
Noguchi Kazuyuki
Publication year - 2021
Publication title -
european journal of oral sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.802
H-Index - 93
eISSN - 1600-0722
pISSN - 0909-8836
DOI - 10.1111/eos.12792
Subject(s) - follistatin , chemistry , bone morphogenetic protein 2 , runx2 , bone morphogenetic protein , periodontal fiber , p38 mitogen activated protein kinases , alkaline phosphatase , endocrinology , medicine , bone morphogenetic protein 7 , bone morphogenetic protein 10 , signal transduction , activin type 2 receptors , downregulation and upregulation , microbiology and biotechnology , kinase , transforming growth factor , protein kinase a , tgf beta signaling pathway , biology , gene , biochemistry , enzyme , dentistry , in vitro
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.