Periodontal ligament cells regulate osteogenesis via miR-299-5p in mesenchymal stem cells

2020 ◽  
Vol 112 ◽  
pp. 47-57 ◽  
Author(s):  
Eri Kaneda-Ikeda ◽  
Tomoyuki Iwata ◽  
Noriyoshi Mizuno ◽  
Takayoshi Nagahara ◽  
Mikihito Kajiya ◽  
...  
2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Huimin Mao ◽  
Andi Yang ◽  
Yunhe Zhao ◽  
Lang Lei ◽  
Houxuan Li

Most mesenchymal stem cells reside in a niche of low oxygen tension. Iron-chelating agents such as CoCl2 and deferoxamine have been utilized to mimic hypoxia and promote cell growth. The purpose of the present study was to explore whether a supplement of succinate, a natural metabolite of the tricarboxylic acid (TCA) cycle, can mimic hypoxia condition to promote human periodontal ligament cells (hPDLCs). Culturing hPDLCs in hypoxia condition promoted cell proliferation, migration, and osteogenic differentiation; moreover, hypoxia shifted cell metabolism from oxidative phosphorylation to glycolysis with accumulation of succinate in the cytosol and its release into culture supernatants. The succinate supplement enhanced hPDLC proliferation, migration, and osteogenesis with decreased succinate dehydrogenase (SDH) expression and activity, as well as increased hexokinase 2 (HK2) and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), suggesting metabolic reprogramming from oxidative phosphorylation to glycolysis in a normal oxygen condition. The succinate supplement in cell cultures promoted intracellular succinate accumulation while stabilizing hypoxia inducible factor-1α (HIF-1α), leading to a state of pseudohypoxia. Moreover, we demonstrate that hypoxia-induced proliferation was G-protein-coupled receptor 91- (GPR91-) dependent, while exogenous succinate-elicited proliferation involved the GPR91-dependent and GPR91-independent pathway. In conclusion, the succinate supplement altered cell metabolism in hPDLCs, induced a pseudohypoxia condition, and enhanced proliferation, migration, and osteogenesis of mesenchymal stem cells in vitro.


2004 ◽  
Vol 83 (1) ◽  
pp. 27-34 ◽  
Author(s):  
P.R. Kramer ◽  
S. Nares ◽  
S.F. Kramer ◽  
D. Grogan ◽  
M. Kaiser

Mesenchymal stem cells differentiate into multiple types of cells derived from mesenchyme. Periodontal ligament cells are primarily derived from mesenchyme; thus, we expected mesenchymal stem cells to differentiate into periodontal ligament. Using a combination of immunohistochemistry and in situ hybridization on co-cultures of mesenchymal stem cells and periodontal ligament, we observed a significant increase in mesenchymal stem cells’ expression of osteocalcin and osteopontin and a significant decrease in expression of bone sialoprotein, characteristics of periodontal ligament in vivo. Increased osteopontin and osteocalcin and decreased bone sialoprotein expression was detected within 7 days and maintained through 21 days of co-culture. We conclude that contact or factors from periodontal ligament induced mesenchymal stem cells to obtain periodontal-ligament-like characteristics. Importantly, analysis of the data suggests the feasibility of utilizing mesenchymal stem cells in clinical applications for repairing and/or regenerating periodontal tissue.


Author(s):  
Sema S. Hakki ◽  
Buket S. Bozkurt ◽  
Erdogan E. Hakki ◽  
Erdal Karaoz ◽  
Ali Unlu ◽  
...  

2009 ◽  
Vol 111 (1) ◽  
pp. 15-24 ◽  
Author(s):  
Monia Orciani ◽  
Oriana Trubiani ◽  
Arianna Vignini ◽  
Monica Mattioli-Belmonte ◽  
R. Di Primio ◽  
...  

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