Molecular and Cellular Biochemistry

, Volume 387, Issue 1–2, pp 27–37 | Cite as

Wnt/β-catenin signaling mediates the senescence of bone marrow-mesenchymal stem cells from systemic lupus erythematosus patients through the p53/p21 pathway

  • Zhifeng GuEmail author
  • Wei Tan
  • Guijuan Feng
  • Yan Meng
  • Biyu Shen
  • Hong Liu
  • Chun ChengEmail author


Recent studies have shown that allogeneic bone marrow (BM)-mesenchymal stem cell transplantation (MSCT) appears to be effective in systemic lupus erythematosus (SLE) patients and lupus-prone mice, contrary to studies in syngeneic BM-MSCT. These studies indicated that the abnormalities of BM-MSCs may be involved in the pathogenesis of SLE. Our studies and other previous studies have revealed that BM-MSCs from SLE patients exhibited early signs of senescence, such as flattened morphology, slow proliferation, increased senescence-associated β-galactosidase (SA-β-gal) activity, and so on. However, the mechanisms by which these cells senescences were still unclear. Previous studies have demonstrated that Wnt/β-catenin signaling plays an important role in stem cell senescence. In the current study, we investigated whether Wnt/β-catenin signaling mediates the senescence of BM-MSCs from SLE patients. We have found that Wnt/β-catenin signaling and the p53/p21 pathway were significantly hyperactivated in senescent SLE BM-MSCs. Treatment with 100 ng/mL Dickkopf-1 (DKK1), a Wnt/β-catenin signaling inhibitor or β-catenin siRNA for 48 h could reverse the senescent features of SLE BM-MSCs. Additionally, the expression levels of p53 and p21 were reduced in treated-SLE BM-MSCs compared with the untreated group. In summary, our study indicated that Wnt/β-catenin signaling may play a critical role in the senescence of SLE BM-MSCs through the p53/p21 pathway.


Bone marrow-mesenchymal stem cells (BM-MSCs) Systemic lupus erythematosus (SLE) Senescence Wnt/β-Catenin signaling p53/p21 pathway 



This study was supported by grants from the Chinese National Natural Science Foundation (Nos. 81172841 and 81202368), China Postdoctoral Science Foundation (2013M541708); the Natural Science Foundation of Jiangsu Colleges and Universities Grant (09KJB320010); the “Top Six Types of Talents” Financial Assistance of Jiangsu Province Grant (No. 6); the project of Jiangsu Provincial Health Department (Z201005); the innovative project of Nantong University postgraduate students (13025043); and the Jiangsu province’s Outstanding Medical Academic Leader Program (LJ201136).


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of RheumatologyAffiliated Hospital of Nantong UniversityNantongChina
  2. 2.Department of StomatologyAffiliated Hospital of Nantong UniversityNantongChina
  3. 3.Department of NursingThe Second Affiliated Hospital of Nantong UniversityNantongChina
  4. 4.Department of HematologyAffiliated Hospital of Nantong UniversityNantongChina
  5. 5.Department of Immunology, Medical College Nantong UniversityNantongChina

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