Effect of FGF-2, TGF-β-1, and BMPs on Teno/Ligamentogenesis and Osteo/Cementogenesis of Human Periodontal Ligament Stem Cells

Abstract

The periodontal ligament (PDL) is the connective tissue between tooth root and alveolar bone containing mesenchymal stem cells (MSC). It has been suggested that human periodontal ligament stem cells (hPDLSCs) differentiate into osteo/cementoblast and ligament progenitor cells. The periodontitis is a representative oral disease where the PDL tissue is collapsed, and regeneration of this tissue is important in periodontitis therapy. Fibroblast growth factor-2 (FGF-2) stimulates proliferation and differentiation of fibroblastic MSCs into various cell lineages. We evaluated the dose efficacy of FGF-2 for cytodifferentiation of hPDLSCs into ligament progenitor. The fibrous morphology was highly stimulated even at low FGF-2 concentrations, and the expression of teno/ligamentogenic markers, scleraxis and tenomodulin in hPDLSCs increased in a dose dependent manner of FGF-2. In contrast, expression of the osteo/cementogenic markers decreased, suggesting that FGF-2 might induce and maintain the ligamentogenic potential of hPDLSCs. Although the stimulation of tenocytic maturation by TGF-β1 was diminished by FGF-2, the inhibition of the expression of early ligamentogenic marker by TGF-β1 was redeemed by FGF-2 treatment. The stimulating effect of BMPs on osteo/cementogenesis was apparently suppressed by FGF-2. These results indicate that FGF-2 predominantly differentiates the hPDLSCs into teno/ligamentogenesis, and has an antagonistic effect on the hard tissue differentiation induced by BMP-2 and BMP-4.

M2 Macrophages Enhance the Cementoblastic Differentiation of Periodontal Ligament Stem Cells via the Akt and JNK Pathways

“…G, H), suggesting the intriguing possibility that JNK signaling may act downstream of the AKT pathway in M2‐enhanced cementoblastic differentiation. Given that cementoblastic differentiation can be regulated by a variety of cytokines, such as BMPs, FGF‐2, TGF‐β, and TNF‐α , and that Mφs can produce a range of proinflammatory mediators (such TNF‐α, IL‐1) or anti‐inflammatory mediators (such TGF‐β, PDGF) to exert protective or pathogenic functions , we continued to explore the mechanisms of M2‐mediated cementoblastic differentiation from the perspective of Mφ‐related cyto‐/chemokines.…”

Gene expression profiling of Jagged1‐treated human periodontal ligament cells

“…TGF‐β1 is multifunctional cytokines that regulate several cellular processes, including morphogenesis, cell differentiation, cell cycle progression, and extracellular matrix production. TGF‐β1 has been shown to regulate differentiation of periodontal ligament cells toward tenocytes, myocytes, and osteoblasts (Hyun, Lee, Kang, & Jang, ; Li & Zhang, ; Xu et al, ). Previous study illustrated that intermittent compressive stress mimicking chewing cycle supregulated sclerostin expression in hPDLs mediated by TGF‐β1 (Manokawinchoke, Sumrejkanchanakij et al, ).…”

Expression dynamics of integrin α2, α3, and αV upon osteogenic differentiation of human mesenchymal stem cells

“…Integrin α3 and αV are upregulated in hPDLCs and hDPCs upon osteogenic differentiation Next, we examined the expression dynamics of integrin α2, α3, and αV in hPDLCs during osteogenic differentiation of hPDLCs. For osteoblastic differentiation of hPDLCs, cells were treated with BMP-2 or ODM-plus BMP-2 as described previously [30]. Relative mRNA expression of bone sialoprotein (BSP), osteocalcin (OC), osteopontin (OP), and Runx2 were increased in BMP-2 and ODM-plus BMP-2 treatment, although relative mRNA expression of ligamentogenic marker scleraxis (SCX) was not altered in ODM-plus BMP-2 treatment (Fig.…”

“…Human periodontal ligament and pulp tissues were separated from the surface of the tooth root and pulp part inside of the tooth after removing tooth crown. Tissues were enzymatically digested with 3 mg/ ml collagenase type I (Merck Millipore, Seoul, Korea) and 4 mg/ml dispase (Sigma-Aldrich, Gyeonggi, Korea) at 37°C for 1 h. Cell suspensions were incubated in α-MEM (GE Healthcare, Seoul, Korea) containing 20% FBS (GE Healthcare) and 1% antibiotics (Lonza, Seoul, Korea) at 37°C in humidified atmosphere supplemented with 5% CO 2 [30,31]. To induce EMT in A549 cells, the cells were plated at 1.8 × 10 4 cells/cm 2 and incubated for 24 h. The cells were then treated with 5 ng/ml of TGF-β1 (Peprotech, Rocky Hill, NJ) for 4 days and the medium was changed every 2 days.…”