Upon transplantation, HPDLSCs co-cultured with DFCs grew well and produced root/periodontal ligament-like and periodontal ligament/bone-like tissues. Several studies have shown that after engraftment, MSCs contribute to tissue repair secretion of trophic molecules, including soluble extracellular matrix glycoproteins, cytokines, and growth factors, and through direct cell-to-cell contact. Moreover, as a type of MSC, DFCs are also young precursor cells. Cells with a young phenotype have been confirmed to enhance the proliferation and differentiation ability of PDLSCs by providing a young microenvironment. However, the environment supplied by DFCs is complicated, which suggests that a combination of multiple factors from DFCs may influence the proliferation and differentiation of HPDLSCs and PPDLSCs, subsequently providing better periodontal regeneration in vivo. In our study, co-culture with DFCs had a greater effect on PPDLSCs than HPDLSCs. Specifically, the stemness-associated gene expression, number of colony-forming units, proliferation index, ALP activity and osteogenic gene expression were all enhanced to a greater degree. Several studies have indicated that, in addition to secreting trophic factors as mentioned above, MSCs also have immunomodulatory and anti-inflammatory properties. MSCs have been shown to modulate the microenvironment of injured tissues and protect damaged tissues by releasing LY2109761 antiinflammatory molecules. These molecules may not only reduce inflammation, apoptosis and fibrosis in damaged tissues but also enhance tissue regeneration. The PPDLSCs in this study were derived from an inflammatory microenvironment. Epigenetics studies have shown that PPDLSCs may constitutively secrete inflammatory factors, such as TNF-a and IL-1b, in vitro. Thus, PPDLSCs are distinct from HPDLSCs with regard to both the cell source and the microenvironment. For example, inflammatory factors secreted by PPDLSCs may stimulate the immunomodulatory effects of DFCs, causing the DFCs to produce more anti-inflammatory cytokines and trophic factors, thereby enhancing the biological properties of the PPDLSCs. Future studies should further explore the specific mechanism. The inactivation of tumor-suppressor genes is a characteristic step in cancer development and progression. Among the mechanisms of tumor-suppressor gene inactivation, aberrant DNA methylation of gene promoter islands and endogenous miRNA upregulation lead to the silencing of tumor-suppressor genes in multiple tissues. The four-and-a-half LIM proteins are a family of LIM-only proteins that regulate cell proliferation, differentiation, and apoptosis. Studies using clinical samples have shown that FHL1 expression is down-regulated in multiple human tumor types, including gastric cancer and hepatocarcinoma. FHL1 exerts tumor suppressor function via multiple mechanisms, including the activation of the TGF-b-like and Src-MAPK signaling pathways and protein interaction with ZO-1, HIF1a, and ERa. Although the role of FHL1 in cancer development and progression is well established.