Yali Liu

Fourth Military Medical University, Xi’an, Liaoning, China

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Publications (5)23.85 Total impact

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    ABSTRACT: Bone extracellular matrix deposition or bone formation by differentiated osteoblasts begins at late stage during bone formation and lasts throughout life. Human mesenchymal stem cells (MSCs) from bone marrow or dental pulp can respectively differentiate into osteoblasts and odontoblasts in vitro. However, the relationship between MSCs and bone/tooth development in cleidocranial dysplasia (CCD) patient is still unclear. In this study, we investigated a patient with CCD, which is an autosomal-dominant, heritable skeletal disease caused by runt-related transcription factor 2 gene (RUNX2) mutation and is characterized by bone and dental anomalies. We found that the mutation is localized at c. 1116_1119insC, p. Q374fsX384 and the proliferative ability and osteogenic potential of the MSCs isolated from the bone marrow and dental pulp of the patient (RUNX2(+/m)) were decreased compared to normal individuals (RUNX2(+/+)). Furthermore, we were unable to recover the differentiation potential of RUNX2(+/m) MSCs isolated from the bone marrow (BMMSCs) upon manipulation of the Wnt/β-catenin pathway, which plays a critical role in stem/progenitor cell self-renewal and adult human MSCs differentiation. In conclusion, we identified a novel insertion/frameshift mutation in the RUNX2 gene that caused a typical CCD phenotype and altered the biological function of RUNX2(+/m) MSCs. The reduced ability of MSCs to differentiate into osteoblasts might provide an explanation for the defects of bone and teeth in the CCD patient. Finally, we demonstrated that manipulation of the Wnt/β-catenin signaling pathway could not overcome this absence.
    European journal of medical genetics 01/2013; · 1.57 Impact Factor
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    ABSTRACT: Inflammatory cytokines, especially TNF-α, have been shown to inhibit osteogenic differentiation of mesenchymal stem cells (MSCs) and bone formation in estrogen deficiency-induced osteoporosis, but the mechanism responsible remains poorly understood. MicroRNAs (miRNAs) have been shown to regulate MSC differentiation. Here, we identified a novel mechanism that TNF-α suppressing the functional axis of a key miRNA(miR-21) contributes to estrogen deficiency-induced osteoporosis. In this study, we screened a key miRNA (miR-21) that was significantly down-regulated in MSCs derived from estrogen deficiency-induced osteoporosis. The miR-21 was suppressed by TNF-α during the osteogenesis of MSCs. Furthermore, miR-21 was confirmed to promote the osteoblast differentiation of MSCs by repressing Spry1, which can negatively regulate the osteogenic differentiation of MSCs. Up-regulating miR-21 partially rescued TNF-α-impaired osteogenesis of MSCs. Blocking TNF-α ameliorated the inflammatory environment and significantly enhanced bone formation with increased miR-21 expression and suppressed Spry1 expression in ovariectomized (OVX) mice. Our results revealed a novel function for miR-21 and suggested that suppressed miR-21 may contribute to impaired bone formation by elevated TNF-α in estrogen deficiency-induced osteoporosis. This study may indicate a molecular basis for novel therapeutic strategies against osteoporosis and other inflammatory bone diseases. © 2012 American Society for Bone and Mineral Research.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 10/2012; · 6.04 Impact Factor
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    ABSTRACT: Chronic inflammatory diseases, such as rheumatoid arthritis and periodontitis, are the most common causes of bone tissue destruction. Recently, human periodontal ligament tissue-derived mesenchymal stem cells (PDLSCs), a population of multipotent stem cells, have been used to reconstruct tissues destroyed by chronic inflammation. However, the impact of the local inflammatory microenvironment on tissue-specific stem cells and the mechanisms controlling the effects of the local inflammatory environment remain poorly understood. In this study, we found that the multidifferentiation potential of mesenchymal stem cells (MSCs) isolated from periodontitis-affected periodontal ligament tissue (P-PDLSCs) was significantly lower than that of MSCs isolated from healthy human periodontal ligament tissue (H-PDLSCs). Inflammation in the microenvironment resulted in an inhibition of miR-17 levels, and a perturbation in the expression of miR-17 partly reversed the differentiation potential of PDLSCs in this microenvironment. Furthermore, inflammation in the microenvironment promoted the expression of Smad ubiquitin regulatory factor one (Smurf1), an important negative regulator of MSC osteogenic differentiation. Western blotting and 3' untranslated regions (3'-UTR) reporter assays confirmed that Smurf1 is a direct target of miR-17 in PDLSCs. Our data demonstrate that excessive inflammatory cytokine levels, miR-17, and Smurf1 were all involved in a coherent feed-forward loop. In this circuit, inflammatory cytokines led to direct activation of Smurf1 and downregulation of miR-17, thereby increasing degradation of Smurf1-mediated osteoblast-specific factors. The elucidation of the molecular mechanisms governing MSC osteogenic differentiation in a chronic inflammatory microenvironment could provide us with a better knowledge of chronic inflammatory disorder and improve stem cell-mediated inflammatory bone disease therapy.
    Stem Cells 09/2011; 29(11):1804-16. · 7.70 Impact Factor
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    ABSTRACT: Periodontal ligament stem cells (PDLSCs), a new population of mesenchymal stem cells (MSCs), have been isolated from the periodontal ligament (PDL). The capacity of multipotency and self-renewal makes them an excellent cell source for bone regeneration and repair. However, their bone-regeneration ability could be awakened in inflammatory microenvironments, which may be the result of changes in their differentiation potential. Recently, genetic evidences has shown that the Wnt pathway plays an important role in bone homeostasis. In this study we have determined the specific role of β-catenin in osteogenic differentiation of PDLSCs obtained from inflammatory microenvironments (P-PDLSCs). The inflammatory microenvironment, while inhibiting osteogenic differentiation potential, promotes proliferation of MSCs. A higher the level of β-catenin in P-PDLSCs than in H-PDLSCs (PDLSCs obtained from a healthy microenvironment) resulted in the same disparity in canonical Wnt signaling pathway activation between each cell type. Here we show that activation of β-catenin suppresses the noncanonical Wnt/Ca(2+) pathway, leading to increased proliferation but reduced osteogenic differentiation of P-PDLSCs. Downregulation of the levels of β-catenin by treatment with dickkopf-1 (DKK-1) leads to activation of the noncanonical Wnt/Ca(2+) pathway, which, in turn, results in the promotion of osteogenic differentiation in P-PDLSCs. Interestingly, β-catenin can affect both the canonical Wnt/β-catenin pathway and the noncanonical Wnt/Ca(2+) pathway. Our data indicate that β-catenin plays a central role in regulating osteogenic differentiation of MSCs in inflammatory microenvironments. Given the important role of Wnt signaling in osteogenic differentiation, it is possible that agents that can modify this pathway may be of value in bone regeneration by MSCs in chronic inflammatory microenvironments.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 06/2011; 26(9):2082-95. · 6.04 Impact Factor
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    ABSTRACT: Hormone deficiency has been recognized as a risk factor for periodontal disease in postmenopausal women. However, the anabolic effects of progesterone on human periodontal ligament cells (hPDLCs) are still unclear. Therefore, the objective of this study was to detect the expression of progesterone receptor (PgR) in hPDLCs and investigate the bone-sparing effects of progesterone. We detected PgR expression in hPDLCs by reverse transcriptase-polymerase chain reaction and immunocytochemistry. After progesterone stimulation, the percentage of hPDLCs entering the S + G2M phase of the cell cycle increased significantly, accompanied by an increased cell growth curve. In both basic culture medium and osteogenic medium, progesterone activated alkaline phosphatase-positive cells and alizarin red-positive nodules. Moreover, mineralization-related markers were up-regulated by progesterone in both time-dependent and dose-dependent manners. In contrast, these effects of progesterone were blocked by the PgR antagonist (RU486). Our results demonstrated that the PgR is expressed in hPDLCs at the gene and protein level, and that progesterone can stimulate the proliferation and differentiation of the hPDLCs. These findings suggest that progesterone may play a significant role in osteoblastic function of hPDLCs and may influence the maintenance of alveolar bone mass.
    Calcified Tissue International 08/2010; 87(2):158-67. · 2.50 Impact Factor

Publication Stats

44 Citations
23.85 Total Impact Points

Institutions

  • 2011–2013
    • Fourth Military Medical University
      • • School of Stomatology
      • • Department of Orthodontics
      Xi’an, Liaoning, China
    • Third Military Medical University
      Ch’ung-ch’ing-shih, Chongqing Shi, China
  • 2012
    • 309th Hospital of the PLA
      Peping, Beijing, China