Function of Chemokine (CXC Motif) Ligand 12 in Periodontal Ligament Fibroblasts

Abstract

The periodontal ligament (PDL) is one of the connective tissues located between the tooth and bone. It is characterized by rapid turnover. Periodontal ligament fibroblasts (PDLFs) play major roles in the rapid turnover of the PDL. Microarray analysis of human PDLFs (HPDLFs) and human dermal fibroblasts (HDFs) demonstrated markedly high expression of chemokine (CXC motif) ligand 12 (CXCL12) in the HPDLFs. CXCL12 plays an important role in the migration of mesenchymal stem cells (MSCs). The function of CXCL12 in the periodontal ligament was investigated in HPDLFs. Expression of CXCL12 in HPDLFs and HDFs was examined by RT-PCR, qRT-PCR and ELISA. Chemotactic ability of CXCL12 was evaluated in both PDLFs and HDFs by migration assay of MSCs. CXCL12 was also immunohistochemically examined in the PDL in vivo. Expression of CXCL12 in the HPDLFs was much higher than that in HDFs in vitro. Migration assay demonstrated that the number of migrated MSCs by HPDLFs was significantly higher than that by HDFs. In addition, the migrated MSCs also expressed CXCL12 and several genes that are familiar to fibroblasts. CXCL12 was immunohistochemically localized in the fibroblasts in the PDL of rat molars. The results suggest that PDLFs synthesize and secrete CXCL12 protein and that CXCL12 induces migration of MSCs in the PDL in order to maintain rapid turnover of the PDL.

Hypoxia-induced upregulation of angiogenic factors in immortalized human periodontal ligament fibroblasts

“…Interestingly, SDF-1α, a protein produced via alternative splicing of the SDF-1 gene, was highly expressed in human PDL fibroblasts. Indeed, the expression level was much higher than that in human dermal fibroblasts (17). Hasegawa et al reported that SDF-1α expression was increased in hPDLF by treatment with transforming growth factor-β1 but inhibited by treatment with basic fibroblast growth factor-2 (18), which suggests that fibroblasts exhibit cell type-specific reactivity to external stimuli.…”

Involvement of the phosphoinositide 3‐kinase/Akt signaling pathway in bone morphogenetic protein 9‐stimulated osteogenic differentiation and stromal cell‐derived factor 1 production in human periodontal ligament fibroblasts

“…Stromal cell‐derived factor 1 is believed to have important roles in recruiting stem/progenitor cells, such as MSCs, to injury sites during tissue repair/regeneration. Periodontal ligament fibroblasts are known to secrete SDF‐1 and the SDF‐1 may induce migration of MSCs to the periodontal ligament in order to maintain rapid turnover of the periodontal ligament . It has been shown that BMP‐9 enhances secretion of SDF‐1 by human bone marrow stem cells .…”

Recruitment of bone marrow‐derived cells to the periodontal ligament via the stromal cell‐derived factor‐1/C‐X‐C chemokine receptor type 4 axis

“…In the present study, we demonstrated that PDL cells synthesize high levels of SDF‐1 and that this synthesis was further increased after tooth replantation in vivo . Similarly, a recent study reported that PDL‐derived cells express SDF‐1 at higher levels than do dermal fibroblasts . These results indicate that high SDF‐1 expression in the PDL may contribute to the migration of BM‐derived stem cells, resulting in the rapid turnover rate of the PDL.…”

“…A recent study reported that PDL‐derived cells express SDF‐1 at high levels ; therefore, we analyzed the concentration of SDF‐1 in PDL cell‐conditioned medium (PDL‐CM). The concentration of SDF‐1 in PDL‐CM was significantly higher than that in control culture medium and osteoblast‐CM (Fig.…”