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.