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

Abstract

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.

Periodontal regeneration following application of basic fibroblast growth factor-2 in combination with beta tricalcium phosphate in class III furcation defects in dogs

“…We attempted to determine the optimal dose of bFGF-2 for periodontal regeneration in dogs from several previous reports. bFGF-2 had a dose-dependent effect on periodontal regeneration at a dose ranging from 0 to 0.16% per implant [3][4][5][6][7][8][9][10][11][12][13][14][15][26][27][28][29] . Hayashi et al reported that new bone formation was smaller in the 0.56% bFGF-2 (100 µg bFGF-2/3×3×2 mm gelatin hydrogel) implant compared to the 0.056% bFGF-2 (10 µg bFGF-2/3×3×2 mm gelatin hydrogel) implant; however, there were no significant differences between them 29) .…”

“…Basic fibroblast growth factor-2 (bFGF-2) is a heparinbinding growth factor that exhibits potent angiogenic activity and mitogenic ability in mesenchymal cells [1][2][3][4][5][6][7] and periodontal ligament cells [8][9][10][11] . Several studies have reported that bFGF-2 induces potent periodontal tissue regeneration along with new alveolar bone and cementum formation without aberrant healing such as root resorption and ankylosis in critical size defects of animal models [12][13][14] .…”

Serum Inter-α-inhibitor Activates the Yes Tyrosine Kinase and YAP/TEAD Transcriptional Complex in Mouse Embryonic Stem Cells

“…Therefore the mechanism through which I␣I can signal to the cells is still not known. It could be related to its binder hyaluronan, as there are several articles that have shown CD44 binding to hyaluronan to be able to induce cell signaling, for example through Akt phosphorylation (48). There is also the possibility of an integrinmediated signaling, using I␣I's ability to bind to vitronectin (34), as integrin-mediated attachment has been also been described to induce cell signaling such as PI3K/Akt phosphorylation (49).…”

Platelet Lysate-Loaded Photocrosslinkable Hyaluronic Acid Hydrogels for Periodontal Endogenous Regenerative Technology

“…In fact, the release of PL-specific GFs from the photocrosslinkable hydrogels, namely FGF-2, was only detected after degradation of the hydrogels in HAase ( Figure 4B), while no detectable traces of GFs were detected after incubation of the hydrogels in PBS. Studies with FGF-2 have shown that this GF upregulate the migration and proliferation of PDL cells 34 . In fact, in order to fully regenerate functional of periodontal tissues, several GFs and cytokines should interplay in a temporal as spatial controlled manner 10 .…”