Fibroblast growth factor-2 stimulates directed migration of periodontal ligament cells via PI3K/AKT signaling and CD44/hyaluronan interaction

J Cell Physiol. 2011 Mar;226(3):809-21. doi: 10.1002/jcp.22406.


Fibroblast growth factor-2 (FGF-2) regulates a variety of functions of the periodontal ligament (PDL) cell, which is a key player during tissue regeneration following periodontal tissue breakdown by periodontal disease. In this study, we investigated the effects of FGF-2 on the cell migration and related signaling pathways of MPDL22, a mouse PDL cell clone. FGF-2 activated the migration of MPDL22 cells and phosphorylation of phosphatidylinositol 3-kinase (PI3K) and akt. The P13K inhibitors, Wortmannin and LY294002, suppressed both cell migration and akt activation in MPDL22, suggesting that the PI3K/akt pathway is involved in FGF-2-stimulated migration of MPDL22 cells. Moreover, in response to FGF-2, MPDL22 showed increased CD44 expression, avidity to hyaluronan (HA) partly via CD44, HA production and mRNA expression of HA synthase (Has)-1, 2, and 3. However, the distribution of HA molecular mass produced by MPDL22 was not altered by FGF-2 stimulation. Treatment of transwell membrane with HA facilitated the migration of MPDL22 cells and an anti-CD44 neutralizing antibody inhibited it. Interestingly, the expression of CD44 was colocalized with HA on the migrating cells when stimulated with FGF-2. Furthermore, an anti-CD44 antibody and small interfering RNA for CD44 significantly decreased the FGF-2-induced migration of MPDL22 cells. Taken together, PI3K/akt and CD44/HA signaling pathways are responsible for FGF-2-mediated cell motility of PDL cells, suggesting that FGF-2 accelerates periodontal regeneration by regulating the cellular functions including migration, proliferation and modulation of extracellular matrix production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / drug effects*
  • Fibroblast Growth Factor 2 / pharmacology*
  • Gene Silencing / drug effects
  • Humans
  • Hyaluronan Receptors / metabolism*
  • Hyaluronic Acid / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Periodontal Ligament / cytology*
  • Periodontal Ligament / drug effects
  • Periodontal Ligament / enzymology
  • Phosphatidylinositol 3-Kinase / metabolism*
  • Phosphorylation / drug effects
  • Protein Binding / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Pseudopodia / drug effects
  • Pseudopodia / metabolism
  • RNA, Small Interfering / metabolism
  • Signal Transduction / drug effects
  • Up-Regulation / drug effects


  • Hyaluronan Receptors
  • RNA, Small Interfering
  • Fibroblast Growth Factor 2
  • Hyaluronic Acid
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt