Canonical Wnt signaling differently modulates osteogenic differentiation of mesenchymal stem cells derived from bone marrow and from periodontal ligament under inflammatory conditions.

Cellular plasticity and complex functional requirements of the periodontal ligament (PDL) assume a local stem cell (SC) niche to maintain tissue homeostasis and repair. Here, pathological alterations caused by inflammatory insults might impact the regenerative capacities of these cells. As bone homeostasis is fundamentally controlled by Wnt-mediated signals, it was the aim of this study to characterize the SC-like capacities of cells derived from PDL and to investigate their involvement in bone pathophysiology especially regarding the canonical Wnt pathway. PDLSCs were investigated for their SC characteristics via analysis of cell surface marker expression, colony forming unit efficiency, proliferation, osteogenic differentiation and adipogenic differentiation, and compared to bone marrow derived mesenchymal SCs (BMMSCs). To determine the impact of both inflammation and the canonical Wnt pathway on osteogenic differentiation, cells were challenged with TNF-α, maintained with or without Wnt3a or DKK-1 under osteogenic induction conditions and investigated for p-IκBα, p-NF-κB, p-Akt, β-catenin, p-GSK-3β, ALP and Runx2. PDLSCs exhibit weaker adipogenic and osteogenic differentiation capacities compared to BMMSCs. TNF-α inhibited osteogenic differentiation of PDLSCs more than BMMSCs mainly through regulating canonical Wnt pathway. Blocking the canonical Wnt pathway by DKK-1 reconstituted osteogenic differentiation of PDLSCs under inflammatory conditions, whereas activation by Wnt3a increased osteogenic differentiation of BMMSCs. Our results suggest a diverse regulation of the inhibitory effect of TNF-α in BMMSCs and PDLSCs via canonical Wnt pathway modulation. These findings provide novel insights on PDLSC SC-like capacities and their involvement in bone pathophysiology under the impact of the canonical Wnt pathway.

Liu W ，Konermann A ，Guo T ，Jäger A ，Zhang L ，Jin Y ... -  《-》

The difference on the osteogenic differentiation between periodontal ligament stem cells and bone marrow mesenchymal stem cells under inflammatory microenviroments.

Periodontitis is a major cause of tooth loss in adults and periodontal ligament stem cells (PDLSCs) is the most favorable candidate for the reconstruction of tissues destroyed by periodontal diseases. However, pathological alterations caused by inflammatory insults might impact the regenerative capacities of these cells. Bone-marrow-derived human mesenchymal stem cells (hBMSCs) would accelerate alveolar bone regeneration by transplantation, compared to PDLSCs. Therefore, a better understanding of the osteogenic differentiation between PDLSCs and BMSCs in inflammatory microenviroments is therefore warranted. In this study, human PDLSCs were investigated for their stem cell characteristics via analysis of cell surface marker expression, colony forming unit efficiency, osteogenic differentiation and adipogenic differentiation, and compared to BMSCs. To determine the impact of both inflammation and the NF-κβ signal pathway on osteogenic differentiation, cells were challenged with TNF-α under osteogenic induction conditions and investigated for mineralization, alkaline phosphatase (ALP) activity, cell proliferation and relative genes expression. Results showed that PDLSCs exhibit weaker mineralization and ALP activity compared to BMSCs. TNF-α inhibited genes expression of osteogenic differentiation in PDLSCs, while, it stimulates gene expressions (BSP and Runx2) in BMSCs. Enhanced NF-κβ activity in PDLSCs decreases expression of Runx2 but it does not impede the osteogenic differentiation of BMSCs. Taken together, these results may suggest that the BMSCs owned the stronger immunomodulation in local microenvironment via anti-inflammatory functions, compared to PDLSCs.

Zhang J ，Li ZG ，Si YM ，Chen B ，Meng J ... -  《-》

Lipopolysaccharide differentially affects the osteogenic differentiation of periodontal ligament stem cells and bone marrow mesenchymal stem cells through Toll-like receptor 4 mediated nuclear factor κB pathway.

Li C ，Li B ，Dong Z ，Gao L ，He X ，Liao L ，Hu C ，Wang Q ，Jin Y ... -  《Stem Cell Research & Therapy》

Nuclear factor-κB modulates osteogenesis of periodontal ligament stem cells through competition with β-catenin signaling in inflammatory microenvironments.

Chen X ，Hu C ，Wang G ，Li L ，Kong X ，Ding Y ，Jin Y ... -  《Cell Death & Disease》

Down-regulated non-coding RNA (lncRNA-ANCR) promotes osteogenic differentiation of periodontal ligament stem cells.

Our studies aimed to figure out how anti-differentiation noncoding RNA (ANCR) regulates the proliferation and osteogenic differentiation of periodontal ligament stem cells (PDLSCs). In this study, we used lentivirus infection to down-regulate the expression of ANCR in PDLSCs. Then we compared the proliferation of control cells and PDLSC/ANCR-RNAi cells by Cell Counting Kit-8. And the osteogenic differentiation of control cells and PDLSC/ANCR-RNAi cells were evaluated by Alkaline phosphatase (ALP) activity quantification and Alizarin red staining. WNT inhibitor was used to analyze the relationship between ANCR and canonical WNT signalling pathway. The expression of osteogenic differentiation marker mRNAs, DKK1, GSK3-β and β-catenin were evaluated by qRT-PCR. The results showed that down-regulated ANCR promoted proliferation of PDLSCs. Down-regulated ANCR also promoted osteogenic differentiation of PDLSCs by up-regulating osteogenic differentiation marker genes. After the inhibition of canonical WNT signalling pathway, the osteogenic differentiation of PDLSC/ANCR-RNAi cells was inhibited too. qRT-PCR results also demonstrated that canonical WNT signalling pathway was activated for ANCR-RNAi on PDLSCs during the procedure of proliferation and osteogenic induction. These results indicated that ANCR was a key regulator of the proliferation and osteogenic differentiation of PDLSCs, and its regulating effects was associated with the canonical WNT signalling pathway, thus offering a new target for oral stem cell differentiation studies that could also facilitate oral tissue engineering.

Jia Q ，Jiang W ，Ni L 《-》