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


METHODS
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.


RESULTS
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.


CONCLUSIONS
Our results suggest a diverse regulation of the inhibitory effect of TNF-α in BMMSCs and PDLSCs via canonical Wnt pathway modulation.


CONCLUSIONS
These findings provide novel insights on PDLSC SC-like capacities and their involvement in bone pathophysiology under the impact of the canonical Wnt pathway.
Research and Development Center for Tissue Engineering, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China; Department of Oral Histology and Pathology, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
Wenjia
W
Liu
Department of Orthodontics, Medical Faculty, University of Bonn, Bonn, Germany.
Anna
A
Konermann
Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
Tao
T
Guo
Department of Orthodontics, Medical Faculty, University of Bonn, Bonn, Germany.
Andreas
A
Jäger
Research and Development Center for Tissue Engineering, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
Liqiang
L
Zhang
Research and Development Center for Tissue Engineering, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China; Department of Oral Histology and Pathology, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China. Electronic address: yanjin@fmmu.edu.cn.
Yan
Y
Jin
D000293:Adolescent; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D007249:Inflammation / Q000473:pathology; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010012:Osteogenesis; D010513:Periodontal Ligament / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D060449:Wnt Signaling Pathway / Q000502:physiology*
D014409:Tumor Necrosis Factor-alpha
ALP; BMMSCs; Bone marrow derived mesenchymal stem cell; Canonical Wnt signaling; Inflammation; LPL; Osteogenesis; PCR; PDLSCs; PPARγ; Periodontal ligament stem cell; Runx2; alkaline phosphatase; bone marrow derived mesenchymal stem cells; lipoprotein lipase; p-Akt; p-GSK-3β; p-IκBα; p-NF-κB; periodontal ligament mesenchymal stem cells; peroxisome proliferator-activated receptor-γ; phosphonated glycogen synthase kinase 3 beta; phosphonated inhibitor of nuclear factor kappa B; phosphonated nuclear factor kappa B; phosphonated v-Akt murine thymoma viral oncogene; polymerase chain reaction; runt-related transcription factor 2