Activation and promotion of adipose stem cells by tumour necrosis factor-α preconditioning for bone regeneration.
There is a major medical need for developing novel and effective approaches for repairing non-union and critical-sized bone defects. Although the mechanisms remain to be determined, it is known that inflammation plays a crucial role in initiating bone repair and regeneration. This study investigated the effect of short-term (3 days) preconditioning with tumor necrosis factor-alpha (TNF-α) on proliferation, mobilization, and differentiation of adipose tissue-derived mesenchymal stem cells (ASCs). We demonstrated that TNF-α pre-conditioning increased proliferation, mobilization, and osteogenic differentiation of ASCs and up-regulated bone morphogenetic protein-2 (BMP-2) protein level. BMP-2 silencing by siRNA partially inhibited osteogenic differentiation of ASCs induced by TNF-α; BMP-2 pre-conditioning also significantly increased osteogenic differentiation of ASCs but the effects were significantly smaller than those observed for TNF-α preconditioning. Furthermore, TNF-α treatment promoted extracellular-signal-regulated kinases(Erk)1/2 and p38 mitogen-activated protein kinase (MAPK) signaling pathways, but only Erk1/2 inhibition reduced the BMP-2 levels and osteogenic differentiation induced by TNF-α preconditioning. Together, these results support the hypothesis that inflammation contributes to bone regeneration by promoting proliferation, mobilization, and osteogenic differentiation of ASCs; 3 days of TNF-α preconditioning, mimicking the short boost of inflammation normally occurring after bone injury, might serve as a feasible approach for directing stem cells into osteogenic differentiation.
Biomaterials and Tissue Engineering Research Unit, School of AMME, the University of Sydney, Sydney, Australia.
Zufu
Z
Lu
Guocheng
G
Wang
Colin R
CR
Dunstan
Yongjun
Y
Chen
William Yenn-Ru
WY
Lu
Ben
B
Davies
Hala
H
Zreiqat
D000273:Adipose Tissue / Q000166:cytology* / Q000473:pathology / Q000502:physiology*; D001861:Bone Regeneration / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D020935:MAP Kinase Signaling System / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism* / Q000502:physiology; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha