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.
OBJECTIVE
The periodontal ligament (PDL) is a non-mineralized connective tissue that exists between the alveolar bone and root surface cementum and plays important roles in tooth function. The PDL harbors a remarkable reserve of multipotent stem cells, which maintain various types of cells. However, the sources of these stem cells, other than their developmental origin, are not well understood.


METHODS
To elucidate the recruitment of bone marrow (BM)-derived stem cells in the PDL, green fluorescent protein (GFP)-expressing BM-derived cells were transplanted into the femoral BM of immunodeficient rats, and the distribution and expression of stem cell markers in the PDL were analyzed in vivo. To evaluate the functional significance of BM-derived cells to the PDL, tooth replantation was performed and the expression of stromal cell-derived factor (SDF)-1, a critical chemotactic signal for mesenchymal stem cell recruitment, was analyzed. To confirm the SDF-1-dependency of BM-derived cell migration to the PDL, PDL-conditioned medium (CM) was prepared, and BM-derived cell migration was analyzed using a transwell culture system.


RESULTS
Four weeks after cell transplantation, GFP-positive cells were detected in the PDL, and some of them were also positive for stem cell markers (i.e., CD29, SSEA4, and αSMA). Seven days after tooth replantation, the number of GFP- and SDF-1-positive cells significantly increased in PDL. Concurrently, the concentration of SDF-1 and the number of colony-forming units of fibroblasts in peripheral blood were increased. BM-derived cell migration increased in PDL-CM and was inhibited by an inhibitor of C-X-C chemokine receptor type 4 (CXCR4), an SDF-1 receptor.


CONCLUSIONS
These results indicate that stem cells and their progeny in PDL are not only derived from their developmental origin but are also supplied from the BM via the blood as the need arises. Moreover, this BM-derived cell recruitment appears to be regulated, at least partially, by the SDF-1/CXCR4 axis.
Division of Bio-Prosthodontics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
M
M
Kaku
Division of Bio-Prosthodontics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
M
M
Kitami
Division of Bio-Prosthodontics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
J M
JM
Rosales Rocabado
Division of Bio-Prosthodontics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
T
T
Ida
Division of Bio-Prosthodontics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Y
Y
Akiba
Division of Bio-Prosthodontics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
K
K
Uoshima
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002465:Cell Movement; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D010513:Periodontal Ligament / Q000166:cytology*; D051381:Rats; D011916:Rats, Inbred F344; D019718:Receptors, CXCR4 / Q000378:metabolism*
C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4
cell recruitment; mesenchymal stem cell; periodontal ligament; stromal cell-derived factor-1/C-X-C chemokine receptor type 4