Released fibroblast growth factor18 from a collagen membrane induces osteoblastic activity involved with downregulation of miR-133a and miR-135a

Kentaro Imamura, Keita Tachi, Tadahiro Takayama, Ryutaro Shohara, Hironori Kasai, Jisen Dai, Seiichi Yamano

Research output: Contribution to journalArticle

Abstract

We have developed a unique delivery system of growth factors using collagen membranes (CMs) to induce bone regeneration. We hypothesized that fibroblast growth factor18 (FGF-18), a pleiotropic protein that stimulates proliferation in several tissues, can be a good candidate to use our delivery system for bone regeneration. Cell viability, cell proliferation, alkaline phosphatase activity, mineralization, and marker gene expression of osteoblastic differentiation were evaluated after mouse preosteoblasts were cultured with a CM containing FGF-18, a CM containing platelet-derived growth factor, or a CM alone. Furthermore, expression of microRNA, especially miR-133a and miR-135a involving inhibition of osteogenic factors, was measured in preosteoblasts with CM/FGF-18 or CM alone. A sustained release of FGF-18 from the CM was observed over 21 days. CM/FGF-18 significantly promoted cell proliferation, alkaline phosphatase activity, and mineralization compared to CM alone. Gene expression of type I collagen, runt-related transcription factor 2, osteocalcin, Smad5, and osteopontin was significantly upregulated in CM/FGF-18 compared to CM alone, and similar to CM/platelet-derived growth factor. Additionally, CM/FGF-18 downregulated expression of miR-133a and miR-135a. These results suggested that released FGF-18 from a CM promotes osteoblastic activity involved with downregulation of miR-133a and miR-135a.

Original languageEnglish (US)
Pages (from-to)1382-1391
Number of pages10
JournalJournal of Biomaterials Applications
Volume32
Issue number10
DOIs
StatePublished - May 1 2018

Keywords

  • Fibroblast growth factor-18
  • bone regeneration
  • collagen membrane
  • microRNA
  • osteoblasts
  • signaling pathway

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering

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