DKK1 rescues osteogenic differentiation of mesenchymal stem cells isolated from periodontal ligaments of patients with diabetes mellitus induced periodontitis.
Multiple studies have shown that diabetes mellitus is an established risk factor for periodontitis. Recently mesenchymal stem cells derived from periodontal ligament (PDLSCs) have been utilized to reconstruct tissues destroyed by chronic inflammation. However, impact of periodontitis with diabetes mellitus on PDLSCs and mechanisms mediating effects of complex microenvironments remain poorly understood. In this study, we found multiple differentiation potential of PDLSCs from chronic periodontitis with diabetes mellitus donors (D-PDLSCs) was damaged significantly. Inhibition of NF-κB signaling could rescue osteogenic potential of PDLSCs from simple chronic periodontitis patients (P-PDLSCs), whereas did not promote D-PDLSCs osteogenesis. In addition, we found expression of DKK1 in D-PDLSCs did not respond to osteogenic signal and decreased osteogenic potential of D-PDLSCs treated with DKK1 could be reversed. To further elucidate different character between P-PDLSCs and D-PDLSCs, we treated PDLSCs with TNF-α and advanced glycation end products (AGEs), and find out AGEs which enhance effect of TNF-α in PDLSCs might mediate special personality of D-PDLSCs. The adverse effect of AGEs in PDLSCs could be reversed when PDLSCs were treated with DKK1. These results suggested DKK1 mediating WNT signaling might be a therapy target to rescue potential of PDLSCs in periodontitis with diabetes mellitus.
1] Department of stomatology, Daping hospital, Research institute of Field surgery, Third military medical university, Chongqing, 400042, China [2] State Key Laboratory of Military Stomatology, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi 710032, China [3] Department of Periodontology, Stomatological hospital, Zunyi medical college, Zunyi, Guizhou 563003, China.
Qi
Q
Liu
1] State Key Laboratory of Military Stomatology, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi 710032, China [2] Xi'an Institute of Tissue Engineering &Regenerative Medicine, Shaanxi 710032, China.
Cheng-Hu
CH
Hu
1] State Key Laboratory of Military Stomatology, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi 710032, China [2] Xi'an Institute of Tissue Engineering &Regenerative Medicine, Shaanxi 710032, China.
Cui-Hong
CH
Zhou
Department of Periodontology, Stomatological hospital, Zunyi medical college, Zunyi, Guizhou 563003, China.
Xiao-Xia
XX
Cui
Department of Periodontology, Stomatological hospital, Zunyi medical college, Zunyi, Guizhou 563003, China.
Kun
K
Yang
Department of Periodontology, Stomatological hospital, Zunyi medical college, Zunyi, Guizhou 563003, China.
Chao
C
Deng
Department of Periodontology, Stomatological hospital, Zunyi medical college, Zunyi, Guizhou 563003, China.
Jia-Jia
JJ
Xia
Department of Periodontology, Stomatological hospital, Zunyi medical college, Zunyi, Guizhou 563003, China.
Yan
Y
Wu
Department of stomatology, Daping hospital, Research institute of Field surgery, Third military medical university, Chongqing, 400042, China.
Lu-Chuan
LC
Liu
1] State Key Laboratory of Military Stomatology, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi 710032, China [2] Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi 710032, China [3] Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Yan
Y
Jin
D000328:Adult; D000368:Aged; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D017127:Glycation End Products, Advanced / Q000494:pharmacology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D010513:Periodontal Ligament / Q000166:cytology*; D010518:Periodontitis / Q000150:complications*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
D050659:Core Binding Factor Alpha 1 Subunit; C501126:DKK1 protein, human; D017127:Glycation End Products, Advanced; D036341:Intercellular Signaling Peptides and Proteins; D016328:NF-kappa B; D016212:Transforming Growth Factor beta; D051176:beta Catenin