Rui Ye

Role of extracellular matrix and YAP/TAZ in cell fate determination

The mechanical signals transduced from cellular microenvironment can regulate cell shape and affect cell fate determination. However, how these mechanical signals are transduced to regulate biological processes of cells has remained elusive. Recent studies had elucidated a novel mechanism through which the interactions between mechanical signals from extracellular matrix and cell behavior regulation converged on the function of core components in Hippo signaling pathway, including YAP and TAZ in mammals. Moreover, several very recent studies have found a new crosstalk between Wnt and Hippo signaling in the regulation of cell fate determination. Such mechanism may explain how mechanical signals from microenvironment can regulate cell behavior and determine cell fate.

MicroRNA control of epithelial-mesenchymal transition in cancer stem cells.

Cancer stem cells (CSCs) represent a small subset of cancer cell populations that possess characteristics associated with normal stem cells. They have the ability to self‐renew, and are able to generate diverse tumor cells and account for metastases. Therefore, CSCs are widely accepted as potential mediators of therapeutic resistance and novel targets for anti‐cancer treatments. Recent progress has highlighted the significance of epithelial–mesenchymal transition (EMT) process in CSC formation, as well as the crucial role of microRNAs in controlling EMT and cancer metastasis. MicroRNAs are also reported to take part in the control of CSC functions and the regulation of cancer progression by affecting EMT process. Thus, it is highly crucial to develop deeper understanding of the mechanisms that how microRNAs control EMT processes and regulate CSC functions for better therapeutics of cancer disease. Herein we make this review to summarize the current understanding of the regulatory mechanisms of EMT in CSC initiation, with a special focus on the role of microRNAs in EMT control, and discuss the implications of targeting CSCs for cancer therapeutics.

The influence of delayed compressive stress on TGF-β1-induced chondrogenic differentiation of rat BMSCs through Smad-dependent and Smad-independent pathways

Mechanical stimuli play important roles in regulating chondrogenic differentiation, but seldom studies have focused on when and how mechanical stimuli should be initiated. We have previously shown that Col2α1 mRNA was increased by delayed dynamic compressive stress initiated at the 8th day of chondrogenic culture. The current work is to further study the possibility of using delayed mechanical stress to relay chondrogenesis initiated by exogenous TGF-β1. Mechanical stimulation was delivered from day 8 to day 14 of chondrogenic culture. It showed that delayed compressive stress not only stimulated gene expression and protein synthesis of chondrocyte-specific markers, but also stimulated the endogenous TGF-β1 gene transcription, protein expression and the subsequent activation even when exogenous TGF-β1 was discontinued. Furthermore, mechanical stress also promoted protein phosphorylation and nuclear translocation of Smad2/3, the TGF-β1 downstream effectors. Inhibition TGF-β with SB431542 significantly affected the stress-induced chondrogenic gene expression. In addition, phosphorylated-p38 and RhoB were upregulated by delayed loading in a TGF-β-related manner. Phosphorylated-ERK1/2 and Wnt7a were also increased, but in a TGF-β-independent way. It indicates that delayed compressive stress can be used as an effective substitute for TGF-β1 supplement in inducing chondrogenic differentiation.

Emerging role of microRNAs in cancer and cancer stem cells.

Cancer stem cells (CSCs), or cancer cells with stem cell properties, represent a small fraction of tumor bulk and are thought to be responsible for tumor formation and metastasis. However, the mechanisms of how CSCs are generated and regulated at the molecular level are poorly understood. Recent progress has highlighted the significance of microRNAs (miRNAs) in cancer progression and CSC function. The function and dysfunction of miRNAs in the development of cancer and CSCs have become a burgeoning area of intense research. A new finding has elucidated a mechanism of antagonistic miRNA crosstalk whereby one miRNA can inhibit another miRNA in regulating CSCs. Herein we make this short review to summarize the current understanding of the regulatory mechanisms of miRNAs in cancer and CSCs and discuss the implications of targeting CSCs for cancer therapeutics. J. Cell. Biochem. 115: 605–610, 2014.

Functional role of mechanosensitive ion channel Piezo1 in human periodontal ligament cells

OBJECTIVE To evaluate the function of Piezo1, an evolutionarily conserved mechanically activated channel, in periodontal ligament (PDL) tissue homeostasis under compressive loading. MATERIALS AND METHODS Primary human PDL cells (hPDLCs) were isolated, cultured, and then subjected to 2.0 g/cm(2) static compressive loading for 0.5, 3, 6, and 12 hours, respectively. The expressions of Piezo1 and osteoclastogenesis marker gene were assessed by semiquantitative reverse transcription-polymerase chain reaction. In addition, Piezo1 inhibitor, GsMTx4, was used to block the function of Piezo1, and tumor necrosis factor-α was also used as a positive control. After 12 hours of compressive loading the PDLCs were co-cultured with murine monocytic cell line RAW264.7. Immunofluorescence, western blot, enzyme-linked immunosorbent assay, and tartrate-resistant acid phosphatase staining were also used to test the potency of PDLCs to induce osteoclastogenesis and the activation of nuclear factor (NF)-κB. RESULTS Piezo1, cyclooxygenase-2, receptor activator of NF-κB ligand, and prostaglandin E2 were significantly upregulated under static compressive stimuli. GsMTx4 repressed osteoclastogenesis in the mechanical stress-pretreated PDLCs-RAW264.7 co-culture system. Furthermore, NF-κB signaling pathway was involved in the mechanical stress-induced osteoclastogenesis. CONCLUSIONS Piezo1 exerts a transduction role in mechanical stress-induced osteoclastogenesis in hPDLCs.

Cell proliferation is promoted by compressive stress during early stage of chondrogenic differentiation of rat BMSCs

The presence of an appropriate number of viable cells is prerequisite for successive differentiation during chondrogenesis. Chondrogenic differentiation has been reported to be influenced by mechanical stimuli. This research aimed to study the effects of cyclic compressive stress on cell viability of rat bone marrow‐derived MSCs (BMSCs) during chondrogenesis as well as its underlying mechanisms. The results showed that dynamic compression increased cell quantity and viability remarkably in the early stage of chondrogenesis, during which the expression of Ihh, Cyclin D1, CDK4, and Col2α1 were enhanced significantly. Possible signal pathways implicated in the process were explored in our study. MEK/ERK and p38 MAPK were not found to function in this process while BMP signaling seemed to play an important role in the mechanotransduction during chondrogenic proliferation. In conclusion, dynamic compressive stress could enhance cell viability during chondrogenesis, which might be achieved by activating BMP signaling. J. Cell. Physiol. 228: 1935–1942, 2013.

Microenvironment Is Involved in Cellular Response to Hydrostatic Pressures During Chondrogenesis of Mesenchymal Stem Cells

Chondrocytes integrate numerous microenvironmental cues to mount physiologically relevant differentiation responses, and the regulation of mechanical signaling in chondrogenic differentiation is now coming into intensive focus. To facilitate tissue‐engineered chondrogenesis by mechanical strategy, a thorough understanding about the interactional roles of chemical factors under mechanical stimuli in regulating chondrogenesis is in great need. Therefore, this study attempts to investigate the interaction of rat MSCs with their microenvironment by imposing dynamic and static hydrostatic pressure through modulating gaseous tension above the culture medium. Under dynamic pressure, chemical parameters (pH, pO2, and pCO2) were kept in homeostasis. In contrast, pH was remarkably reduced due to increased pCO2 under static pressure. MSCs under the dynamically pressured microenvironment exhibited a strong accumulation of GAG within and outside the alginate beads, while cells under the statically pressured environment lost newly synthesized GAG into the medium with a speed higher than its production. In addition, the synergic influence on expression of chondrogenic genes was more persistent under dynamic pressure than that under static pressure. This temporal contrast was similar to that of activation of endogenous TGF‐β1. Taken altogether, it indicates that a loading strategy which can keep a homeostatic chemical microenvironment is preferred, since it might sustain the stimulatory effects of mechanical stimuli on chondrogenesis via activation of endogenous TGF‐β1. J. Cell. Biochem. 115: 1089–1096, 2014.

Mechanotransduction in cancer stem cells

The cancer stem cell (CSC) concept, which arose about a decade ago, proposes that tumor growth is sustained by a subpopulation of highly malignant cells. These cells, termed CSCs, are capable of extensive self‐renewal that contributes to metastasis and treatment resistance. Therefore, therapeutic strategies that target CSCs should be developed for improving outcomes of cancer patients. Recent progress has highlighted the importance of physical properties of the extracellular matrix and mechanotransduction pathway in cancer cells during cancer development. On the other hand, the significance of CXCR1, an upstream signal of FAK/PI3K/Akt has been revealed in CSCs. FAK/PI3K/Akt is a key signal mediator in mechanotransduction pathway. Therefore, mechanotransduction could be a new target for CSCs, and would be an innovative way to treat cancer by inhibiting FAK/PI3K/Akt.

Occlusal plane canting reduction accompanies mandibular counterclockwise rotation in camouflaging treatment of hyperdivergent skeletal Class II malocclusion

OBJECTIVE To investigate the occlusal configurations of the hyperdivergent skeletal Class II malocclusion and their alterations during the camouflaging treatment in an attempt to identify occlusal changes that might be related to mandibular counterclockwise rotation. MATERIALS AND METHODS Cephalograms of 126 subjects with hyperdivergent skeletal Class II malocclusion and 126 subjects with a clinically normal skeletal pattern were chosen. Several measurements were calculated and compared between the groups. To examine the effects of treatment, two groups were established according to mandibular rotation: counterclockwise rotation (CCR) and the opposite clockwise rotation (CR). After 40 subjects were excluded, the other 86 Class II subjects were assigned to CCR (n = 22) and CR (n = 64). Their pretreatment (T1), posttreatment (T2), and postretention (T3) cephalograms were obtained. Measurement changes (T3-T1) were analyzed in each group and compared between groups. RESULTS Compared with the normal skeletal pattern, the cant of the occlusal plane (OP) of the study subjects was significantly steeper and the vertical heights of the incisors were significantly larger for the malocclusion. Compared with the changes in CR, there was a prominent reduction of the OP canting with remarkable intrusion of the maxillary incisor in CCR. CONCLUSION Increased OP canting with overerupted incisors is evident in the hyperdivergent skeletal Class II malocclusion. During the camouflaging treatment, reduction of OP canting could occur. It was accompanied by mandibular counterclockwise rotation and intrusion of the maxillary incisor.

Primary dysmenorrhea is potentially predictive for initial orthodontic pain in female patients

OBJECTIVE To investigate the relationship between primary dysmenorrhea (PD) and orthodontic pain in female patients, and to test the hypothesis that the intensity and duration of orthodontic pain could be roughly predicted by severity of PD. MATERIALS AND METHODS One hundred twenty college females were enrolled and put into one of three groups-mild (Mi), moderate (Mo), or severe (S)-according to level of menstrual pain. Intensity of the orthodontic pain was measured by visual analog scale (VAS) on days 1, 2, 4, 7, 14, and 28 after archwire placement. RESULTS As the intensity of orthodontic pain declined with time, the three groups demonstrated different changes during the initial week. Mi had the lowest VAS scores, whereas S possessed the highest scores. In contrast, Mo stayed in between. Significantly positive correlations were found between the severity of PD and the intensity of orthodontic pain at each time point within the first 2 weeks. In addition, though the majority of subjects reported disappearance of pain by the end of the second week in both Mi and Mo, a large proportion of females still perceived pain in S. CONCLUSION Females with higher levels of menstrual pain tended to perceive orthodontic pain with higher intensity and more prolonged duration. Thus, PD could potentially serve as a reference to predict orthodontic pain in clinical settings.