Humoral factors released from human periodontal ligament cells influence calcification and proliferation in human bone marrow mesenchymal stem cells.
BACKGROUND
Transplantation of bone marrow mesenchymal stem cells (MSCs) is believed to be a new modality for periodontal tissue regeneration. However, little is known about the factors that influence the functions of the transplanted MSCs. Periodontal ligament cells may be implicated in regulating MSC functions.


METHODS
To examine the effect of humoral factors (HFs) produced by human periodontal ligament (HPL) cells on human MSC (hMSC) gene expression, hMSCs were cocultured separately with HPL cells. The gene expression of the hMSCs was analyzed by microarray. Moreover, the effect of conditioned medium (CM) from cultures of HPL cells (CM-HPL cells) on the proliferation and mineralizing capacity of hMSCs was examined.


RESULTS
Thirty-five genes whose expressions were upregulated more than two-fold and 32 genes whose expressions were downregulated more than two-fold were identified in hMSCs cocultured separately with HPL cells. CM-HPL cells prevented calcification in hMSCs cultured with bone morphogenetic protein-2 but not dexamethasone. CM-HPL cells stimulated cell proliferation in hMSCs, whereas CM from culture of human osteoblasts did not influence the proliferation.


CONCLUSIONS
To the best of our knowledge, this is the first study on the global gene expression of MSCs cocultured with periodontal ligament cells. A particular humoral factor released from periodontal ligament cells is suggested to affect differentiation and proliferation in MSCs.
Mizuno
Noriyoshi
N
Department of Periodontal Medicine, Division of Frontier Medical Science, Hiroshima University Graduate School of Biomedical Sciences, Kasumi, Hiroshima, Japan. mizuno@hiroshima-u.ac.jp
Ozeki
Yoshitaka
Y
Shiba
Hideki
H
Kajiya
Mikihito
M
Nagahara
Takayoshi
T
Takeda
Katsuhiro
K
Kawaguchi
Hiroyuki
H
Abiko
Yoshimitsu
Y
Kurihara
Hidemi
H
D000293:Adolescent; D000328:Adult; D001854:Bone Marrow Cells / Q000187:drug effects / Q000502:physiology*; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D002113:Calcification, Physiologic / Q000187:drug effects / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000032:analysis; D051796:Inhibitor of Differentiation Proteins / Q000032:analysis; D020738:Leptin / Q000032:analysis; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000502:physiology*; D046228:Microarray Analysis; D009363:Neoplasm Proteins / Q000032:analysis; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology; D010513:Periodontal Ligament / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D017077:Culture Media, Conditioned; D005938:Glucocorticoids; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D051796:Inhibitor of Differentiation Proteins; D020738:Leptin; D009363:Neoplasm Proteins; C075640:ID3 protein, human; D003907:Dexamethasone