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

• Published in: Biochimica et biophysica acta Vol. 1840; no. 3; pp. 1125 - 1134
• Main Authors: Liu, Wenjia, Konermann, Anna, Guo, Tao, Jäger, Andreas, Zhang, Liqiang, Jin, Yan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2014
• Subjects: adipogenesis; Adolescent; bone formation; bone marrow; Bone Marrow Cells - cytology; Bone marrow derived mesenchymal stem cell; Canonical Wnt signaling; Cell Differentiation; Cells, Cultured; homeostasis; Humans; Inflammation; Inflammation - pathology; ligaments; Mesenchymal Stem Cells - cytology; Osteogenesis; pathophysiology; Periodontal Ligament - cytology; Periodontal ligament stem cell; stem cells; tumor necrosis factor-alpha; Tumor Necrosis Factor-alpha - pharmacology; Wnt Signaling Pathway - physiology; BMMSCs; ALP; LPL; Inflammation; Bone marrow derived mesenchymal stem cell; Periodontal ligament stem cell; PDLSCs; PPARγ; p-NF-κB; p-Akt; p-GSK-3β; p-IκBα; Canonical Wnt signaling; PCR; Osteogenesis; Runx2; phosphonated v-Akt murine thymoma viral oncogene; runt-related transcription factor 2; phosphonated nuclear factor kappa B; bone marrow derived mesenchymal stem cells; alkaline phosphatase; polymerase chain reaction; peroxisome proliferator-activated receptor-γ; phosphonated inhibitor of nuclear factor kappa B; lipoprotein lipase; phosphonated glycogen synthase kinase 3 beta; periodontal ligament mesenchymal stem cells
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2013.11.003

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. •Multi-lineage differentiation capacity is more distinct in BMMSCs than in PDLSCs.•TNF-α inhibits osteogenic differentiation of PDLSCs stronger than BMMSCs.•Canonical Wnt pathway and TNF-α oppositely modulate osteogenic SC differentiation.•DKK-1 reconstitutes PDLSC osteogenic differentiation under inflammatory conditions.•Wnt3a increases BMMSC osteogenic differentiation under inflammatory conditions.