EIF3D promoted cervical carcinoma through Warburg effect by interacting with GRP78.

The incidence of cervical cancer ranks third among all female tumours globally and second in developing countries. However, the role of eukaryotic translation initiation factor 3 subunit D (EIF3D) in cervical carcinoma is unknown. This study investigated the effects of EIF3D on cell progression of cervical carcinoma and its underlying mechanism in vivo and vitro models. There were increases of EIF3D expression mRNA and protein expression levels in patients with cervical carcinoma. Disease-free survival (DFS) and overall surviva (OS) of EIF3D lower expression in patients with cervical carcinoma was higher than those of EIF3D higher expression. EIF3D mRNA expression levels in cervical carcinoma cell lines (AV3, Hela229, CaSki and Hela cells) were up-regulated, compared with cervical normal cell line (UVECs). EIF3D promoted cell growth and Warburg effect in vitro model of cervical carcinoma. EIF3D interacting with GRP78 to reduce the activity of GRP78 in vitro model of cervical carcinoma. The inhibition of GRP78 reduced the effects of EIF3D on Warburg effect in vitro model of cervical carcinoma.Our work identifies EIF3D promoted cell growth and Warburg effect in vitro model of cervical carcinoma and the inhibition of EIF3D represents a potential therapeutic strategy for the treatment of cervical carcinoma.IMPACT STATEMENTWhat is already known on this subject? The incidence of cervical cancer ranks third among all female tumours globally and second in developing countries.What do the results of this study add? This study investigated the effects of EIF3D on cell progression of cervical carcinoma and its underlying mechanism in vivo and vitro models.What are the implications of these findings for clinical practice and/or further research? EIF3D promoted cell growth and Warburg effect in vitro model of cervical carcinoma and the inhibition of EIF3D represents a potential therapeutic strategy for the treatment of cervical carcinoma.

Corrigendum: Role of TGF-ß/Smad Pathway in the Transcription of Pancreas-Specific Genes During Beta Cell Differentiation.

[This corrects the article DOI: 10.3389/fcell.2019.00351.].

Long Non-coding RNA Maternally Expressed 3 Increases the Expression of Neuron-Specific Genes by Targeting miR-128-3p in All-Trans Retinoic Acid-Induced Neurogenic Differentiation From Amniotic Epithelial Cells.

MicroRNA (miR)-128-3p is a brain-enriched miRNA that participates in the regulation of neural cell differentiation and the protection of neurons, but the mechanisms by which miR-128-3p regulates its target and downstream genes to influence cell fate from adult stem cells are poorly understood. In this study, we show down-regulation of miR-128-3p during all-trans retinoic acid (ATRA)-induced neurogenic differentiation from amniotic epithelial cells (AECs). We investigated miR-128-3p in both the Notch pathway and in the expression of neuron-specific genes predicted to be involved in miR-128-3p signaling to elucidate its role in the genetic regulation of downstream neurogenic differentiation. Our results demonstrate that miR-128-3p is a negative regulator for the transcription of the neuron-specific genes ß III-tubulin, neuron-specific enolase (NSE), and polysialic acid-neural cell adhesion molecule (PSA-NCAM) via targeting Jagged 1 to inhibit activation of the Notch signaling pathway. We also used bioinformatics algorithms to screen for miR-128-3p interactions with long non-coding (lnc) RNA and circular RNA as competing endogenous RNAs to further elucidate underlying down-regulated molecular mechanisms. The lncRNA maternally expressed 3 is up-regulated by the ATRA/cAMP/CREB pathway, and it, in turn, is directly down-regulated by miR-128-3p to increase the amount of neuron differentiation. Endogenous miRNAs are, therefore, involved in neurogenic differentiation from AECs and should be considered during the development of effective cell transplant therapies for the treatment of neurodegenerative disease.

Role of TGF-ß/Smad Pathway in the Transcription of Pancreas-Specific Genes During Beta Cell Differentiation.

Autoimmune destruction of pancreatic beta cells causes absolute insulin deficiency and results in type 1 diabetes mellitus (T1DM). The substitution of healthy pancreatic beta cells for damaged cells would be the ideal treatment for T1DM; thus, the generation of pancreatic beta cells from adult stem cells represents an attractive avenue for research. In this study, a cocktail of factors was used to induce the differentiation of pancreatic beta cells from mesenchymal stem cells (MSCs). The differentiation program was divided into five stages, and the roles of the cocktail factors used during each stage were systematically elucidated. Activin A was found to phosphorylate Smad2 and Smad3 in stage III, thereby activating the TGF-ß/Smad pathway. Meanwhile, the endocrine-specific transcription factor, Ngn3, and the pancreas-specific miRNAs, miR-375 and miR-26a, were dramatically elevated in stage III. We next demonstrated that Smad4, an important transcription factor in the TGF-ß/Smad pathway, could bind to the promoter sequences of target genes and enhance their transcription to initiate the differentiation of beta cells. Use of SB-431542, an inhibitor of the TGF-ß/Smad pathway, demonstrated in vivo and in vitro that this pathway plays a critical role in the production of pancreatic beta cells and in modulating insulin secretion. Thus, the TGF-ß/Smad pathway is involved in the production of beta cells from adult stem cells by enhancing the transcription of Ngn3, miR-375, and miR-26a. These findings further underline the significant promise of cell transplant therapies for type 1 diabetes mellitus.

Knockdown of Bone Morphogenetic Proteins Type 1a Receptor (BMPR1a) in Breast Cancer Cells Protects Bone from Breast Cancer-Induced Osteolysis by Suppressing RANKL Expression.

BACKGROUND/AIMS: Bone morphogenetic proteins (BMPs) and BMP receptors widely participate in osteolytic metastasis of breast cancer, while their role in tumor-stromal interaction is largely unknown. In this study, we investigated whether BMP receptor type 1a (BMPR1a) can alter the interaction between metastatic cancer cells and osteoclast precursors. METHODS: Adenovirus-mediated RNA interference was used to interrupt target genes of human breast cancer cell lines and nude mice were injected intratibially with the cancer cells. Tumor-bearing mice were examined by bioluminescence imaging and microCT. Sections of metastatic legs were measured by a series of staining methods. Murine bone marrow mononuclear cells or RAW264.7 cells were cultured with conditioned media of breast cancer cells. RT-PCR, Western blotting and ELISA were used to test mRNA and protein expressions of target molecules. RESULTS: Expression of BMPR1a of MDA-MB-231-luc cells at tumor-bone interface was apparently stronger than that of cancer cells distant from the interface. Mice injected with BMPR1a-knockdown MDA-MB-231-luc cells showed reduced tumor growth and bone destruction compared with control groups. Knockdown (KD) of BMPR1a of MDA-MB-231-luc cells or MCF-7 cells decreased the level of receptor activator for NF-κB ligand (RANKL). Level of RANKL in MDA-MB-231-luc cells or MCF-7 cells was reduced by p38 inhibitor. Compared with control group, knockdown of p38 of breast cancer cells decreased cancer-induced osteoclastogenesis. CONCLUSION: Knockdown of BMPR1a of breast cancer cells suppresses their production of RANKL via p38 pathway and inhibits cancer-induced osteoclastogenesis, which indicates that BMPR1a might be a possible target in breast cancer-induced osteolytic metastasis.

Novel posterior artificial atlanto-odontoid joint for atlantoaxial instability: a biomechanical study.

OBJECTIVE Atlantoaxial instability is usually corrected by anterior and/or posterior C1-2 fusion. However, fusion can lead to considerable loss of movement at the C1-2 level, which can adversely impact a patient's quality of life. In this study, the authors investigated the stability and function of a novel posterior artificial atlanto-odontoid joint (NPAAJ) by using cadaveric cervical spines. METHODS The Oc-C7 regions from 10 cadaveric spines were used for anteroposterior (AP) translation and range of motion (ROM) tests while intact and after destabilization, NPAAJ implantation, and double-rod fixation. RESULTS The mean AP C1-2 translational distances in the intact, destabilization, and double-rod groups were 6.53 ± 1.07 mm, 11.54 ± 1.59 mm, and 3.24 ± 0.99 mm, respectively, and the AP translational distance in the NPAAJ group was significantly different from that in the intact group (p < 0.05). The AP translational distance in the NPAAJ group was not significantly different from that in the double-rod group (p = 0.24). The mean flexion, extension, and axial rotation ROM values of the NPAAJ group were 9.87° ± 0.91°, 8.75° ± 0.99°, and 61.93° ± 2.93°, respectively, and these were lower than the corresponding values in the intact group (p < 0.05). The mean lateral bending ROM in the NPAAJ group (9.26° ± 0.86°) was not significantly different from that in the intact group (p = 0.23), and the flexion, extension, and rotation ranges in the NPAAJ group were 79.5%, 85.2%, and 82.3%, respectively, of those in the intact group. CONCLUSIONS Use of NPAAJ for correction of atlantoaxial instability disorders caused by congenital odontoid dysplasia, odontoid fracture nonunion, and C-1 transverse ligament disruption (IA, IB, and IIB) may restore the stability and preserve most of the ROM of C1-2. Additionally, the NPAAJ may prevent soft tissue from embedding within the joint. However, additional studies should be performed before the NPAAJ is used clinically.

miR­494 inhibits cell proliferation and metastasis via targeting of CDK6 in osteosarcoma.

Tumorigenesis is a multistep process involving various cell growth­associated factors. Accumulated evidence indicates that the disordered regulation of microRNAs (miRNAs) contributes to tumorigenesis. However, the detailed mechanism underlying the involvement of miRNAs in oncogenesis remains to be fully elucidated. In the present study, the repressed expression of microRNA (miR)­494 was identified in 18 patients with osteosarcoma (OS) and OS cell lines, compared with corresponding controls. To determine whether deregulated miR­494 exerts tumor­suppressive effects in the development of OS, the effects of miR­494 on cell proliferation and metastasis were evaluated. It was found that the restoration of miR­494 in MG­63 and U2OS cells led to inhibited cell proliferation and attenuated migratory propensity in vitro, determined through analysis using MTT, colony formation and Transwell assays. In addition, overexpression of miR­494 markedly suppressed the tumor volume and weight in vivo. In accordance, the ectopic expression of miR­494 induced cell cycle arrest at the G1/S phase in OS cells. Bioinformatics analysis and luciferase reporter assays were performed to investigate the potential regulatory role of miR­494, the results of which indicated that miR­494 directly targeted cyclin­dependent kinase 6 (CDK6). Of note, the data obtained through reverse transcription­quantitative polymerase chain reaction and western blot analyses suggested that the elevated expression of miR­494 resulted in reduced mRNA and protein expression levels of CDK6. Taken together, these findings indicated that the miR­494/CDK6 axis has a significant tumor­suppressive effect on OS, and maybe a diagnostic and therapeutic target for the treatment of OS.

Biomechanical study of novel unilateral C1 posterior arch screws and C2 laminar screws combined with an ipsilateral crossed C1-C2 pedicle screw-rod fixation for atlantoaxial instability.

INTRODUCTION: Current surgical methods to treat atlantoaxial instability pose potential risks to the surrounding blood vessels and nerves of operative approach. Therefore, more secure and highly effective methods are expected. This study sought to assess the biomechanical efficacy of a novel unilateral double screw-rod fixation system by comparing with traditional and emerging fixation methods in cadaveric models. MATERIALS AND METHODS: Ligamentous cervical spines (C0-C7) from ten fresh cadaveric specimens were used to complete range of motion (ROM) test in their intact condition (control group), destabilization, and stabilization after different fixations, including unilateral C1-C2 pedicle screws (PS) with a screw-rod system (Group A), bilateral C1-C2 PS with screw-rod systems (Group B), unilateral C1 posterior arch screws (PAS) and C2 laminar screws (LS) combined with an ipsilateral paralleled C1-C2 PS-rod (Group C), and unilateral C1 PAS and C2 LS combined with an ipsilateral crossed C1-C2 PS-rod (Group D). After that, pullout strength test was performed between PS and PAS using ten isolated atlas vertebras. RESULTS: All fixation groups reduced flexibility in all directions compared with both control group and destabilization group. Furthermore, comparisons among different fixation groups showed that bilateral C1-C2 PS-rod (Group B), unilateral C1 PAS + C2 LS combined with an ipsilateral paralleled C1-C2 PS-rod (Group C) and unilateral C1 PAS + C2 LS combined with an ipsilateral crossed C1-C2 PS-rod (Group D) could provide a better stability, respectively, in all directions than unilateral C1-C2 PS-rod (Group A). However, no statistical significance was observed among Groups B, C, and D. Data from pullout strength test showed that both C1 PS (585 ± 53 N) and PAS (463 ± 49 N) could provide high fixed strength, although PS was better (P = 0.009). CONCLUSION: The surgical technique of unilateral C1 PAS + C2 LS combined with a ipsilateral crossed C1-C2 PS-rod fixation could provide a better stability than the traditional unilateral PS-rod fixation and a same stability as bilateral PS-rod fixation, but with less risk of neurovascular injury. Therefore, this new technique may provide novel insight for an alternative of atlantoaxial instability treatment.

Tetrandrine inhibits the proliferation of human osteosarcoma cells by upregulating the PTEN pathway.

Tetrandrine (TET) is a natural product isolated from the Chinese herb Stephania tetrandra S. Moore and has been reported to have antiproliferation and apoptosis-inducing activity in various malignant tumor cells. However, the exact molecular mechanisms underlying these effects remain unclear. In the present study, we tested the antiproliferation effect of TET on osteosarcoma (OS) 143B cells and explored the possible potential molecular mechanism in this process. Using CCK-8 assay and flow cytometry, we found that TET inhibited proliferation, induced apoptosis and arrested the cell cycle of the 143B cells. Using a xenograft tumor model of human OS, tetrandrine was found to inhibit tumor growth in vivo. TET increased the protein level of phosphatase and tensin homolog (PTEN) and decreased its phosphorylation as detected by western blot analysis and immunohistochemistry.Overexpression of PTEN strengthened the anticancer effect of TET, while knockdown of PTEN attenuated it. Meanwhile, TET activated p38 MAPK and increased its phosphorylation. Our findings suggest that TET may be a potential anticancer drug for OS. In addition, its effects may be mediated by the upregulation of PTEN. Moreover the expression alteration of PTEN and p-PTEN was mediated by the TET-induced activation of p38 MAPK in a direct or indirect manner.

Ursolic acid inhibits proliferation and induces apoptosis by inactivating Wnt/ß-catenin signaling in human osteosarcoma cells.

Although multiple chemotherapeutic agents have been used for osteosarcoma (OS) treatment, their mechanisms need further study. Ursolic acid (UA), a pentacyclic triterpenoid, can reduce cell proliferation and induce apoptosis in various cancer cells, such as OS. However, the exact mechanism underlying this function remains unclear. In this study, we investigated the anti­proliferative effect of UA in human OS 143B cells and dissected the possible molecular mechanism underlying this effect. We demonstrated that UA can reduce cell proliferation, induce apoptosis and arrest cell cycle in 143B cells, as well as inhibit OS tumor growth in a mouse xenograft model. Using a luciferase reporter assay, we found that the Wnt/ß­catenin signaling is inhibited by UA in 143B cells. Correspondingly, the expression level and nuclear translocation of ß­catenin are both decreased by UA. Exogenous expression of ß­catenin attenuates the anticancer effect of UA in 143B cells, while knockdown of ß­catenin enhances this effect. UA increases the expression level of p53 in a concentration­dependent manner, and inhibition of p53 reduces the anticancer effect of UA in 143B cells. Moreover, inhibition of p53 partly reverses the UA­induced downregulation of ß­catenin, as do the targets of Wnt/ß­catenin signaling, such as c­Myc and cyclin D1. Our findings indicated that UA can inhibit the proliferation of 143B OS cells through inactivation of Wnt/ß-catenin signaling, which may be mediated partly by upregulating the expression of p53.

Adenovirus-mediated siRNA targeting CXCR2 attenuates titanium particle-induced osteolysis by suppressing osteoclast formation.

BACKGROUND Wear particle-induced peri-implant loosening is the most common complication affecting long-term outcomes in patients who undergo total joint arthroplasty. Wear particles and by-products from joint replacements may cause chronic local inflammation and foreign body reactions, which can in turn lead to osteolysis. Thus, inhibiting the formation and activity of osteoclasts may improve the functionality and long-term success of total joint arthroplasty. The aim of this study was to interfere with CXC chemokine receptor type 2 (CXCR2) to explore its role in wear particle-induced osteolysis. MATERIAL AND METHODS Morphological and biochemical assays were used to assess osteoclastogenesis in vivo and in vitro. CXCR2 was upregulated in osteoclast formation. RESULTS Local injection with adenovirus-mediated siRNA targeting CXCR2 inhibited titanium-induced osteolysis in a mouse calvarial model in vivo. Furthermore, siCXCR2 suppressed osteoclast formation both directly by acting on osteoclasts themselves and indirectly by altering RANKL and OPG expression in osteoblasts in vitro. CONCLUSIONS CXCR2 plays a critical role in particle-induced osteolysis, and siCXCR2 may be a novel treatment for aseptic loosening.

IGF1 potentiates BMP9-induced osteogenic differentiation in mesenchymal stem cells through the enhancement of BMP/Smad signaling.

Engineered bone tissue is thought to be the ideal alternative for bone grafts in the treatment of related bone diseases. BMP9 has been demonstrated as one of the most osteogenic factors, and enhancement of BMP9-induced osteogenesis will greatly accelerate the development of bone tissue engineering. Here, we investigated the effect of insulin-like growth factor 1 (IGF1) on BMP9-induced osteogenic differentiation, and unveiled a possible molecular mechanism underling this process. We found that IGF1 and BMP9 are both detectable in mesenchymal stem cells (MSCs). Exogenous expression of IGF1 potentiates BMP9-induced alkaline phosphatase (ALP), matrix mineralization, and ectopic bone formation. Similarly, IGF1 enhances BMP9-induced endochondral ossification. Mechanistically, we found that IGF1 increases BMP9-induced activation of BMP/Smad signaling in MSCs. Our findings demonstrate that IGF1 can enhance BMP9-induced osteogenic differentiation in MSCs, and that this effect may be mediated by the enhancement of the BMP/Smad signaling transduction triggered by BMP9. [BMB Reports 2016; 49(2): 122-127].

Evodiamine inhibits the proliferation of human osteosarcoma cells by blocking PI3K/Akt signaling.

Osteosarcoma (OS) is the most common non-hematologic primary malignancy of bone, and multiple chemotherapeutic agents have been applied in the treatment of OS for over 40 years. Nevertheless, due to the poor prognosis of OS, it is essential to develop a novel treatment strategy. Evodiamine (EVO), a quinolone alkaloid extracted from the fruit of Evodia rutaecarpa, has been demonstrated to inhibit tumor cell proliferation. Thus, the main aim of the present study was to investigate the anti-proliferative and apoptosis-inducing effects of evodiamine (EVO) on human OS 143B cells, but also the possible mechanisms underlying these effects. The results of crystal violet staining, flow cytometry, western blot analysis and an in vivo experiment demonstrated that EVO exhibits significant inhibitory effects on cell proliferation, exhibits apoptosis-inducing effects and arrests the cell cycle in 143B cells. According to our findings of polymerase chain reaction (PCR), western blot analysis and recombinant adenoviral transfection, we confirmed that EVO upregulates both the protein and gene levels of phosphatase and tensin homolog (PTEN) in a concentration-dependent manner in 143B cells. Overexpression of PTEN reinforced the anti-proliferative effect of EVO in the 143B cells, while knockdown of PTEN upregulated PI3K/Akt signaling transduction and reversed the inhibitory effect of EVO on 143B cell proliferation. Further analysis indicated that EVO upregulated the expression of PTEN by inactivating PI3K/Akt signaling by decreasing phosphorylated Akt1/2. Based on the above results, we conclude that PTEN/PI3K/Akt signaling is involved in the inhibitory effect on human OS 143B cell proliferation by EVO.

Oridonin inhibits the proliferation of human osteosarcoma cells by suppressing Wnt/ß-catenin signaling.

It has been reported that oridonin (ORI) can inhibit proliferation and induce apoptosis in various types of cancer cell lines. However, the exact mechanism for this function remains unclear. In this study, we investigated the proliferation inhibitory effect of ORI on human osteosarcoma (OS) 143B cells and dissected the possible molecular mechanism(s) underlying this effect. We demonstrated that ORI can inhibit proliferation, induce apoptosis and arrest the cell cycle in 143B cells. Using luciferase reporter assay, we found that the Wnt/ß-catenin signaling was inhibited in 143B cells by ORI. Accordingly, the total protein levels and nuclear translocation of ß-catenin were reduced by ORI treatment. ORI increased glycogen synthase kinase 3ß (GSK3ß) activity and upregulated Dickkopf-1 (Dkk-1) expression. We found that Dkk-1 overexpression or ß-catenin knockdown can potentiate the proliferation inhibitory effect of ORI in 143B cells, while ß-catenin overexpression attenuated this effect. Using the xenograft tumor model of human OS, we demonstrated that ORI effectively inhibited the growth of tumors. Histological examination showed that ORI inhibited cancer cell proliferation, decreased the expression of PNCA and ß-catenin. Our findings suggest that ORI can inhibit 143B OS cell proliferation by downregulating Wnt/ß-catenin signal transduction, which may be mediated by upregulating the Dkk-1 expression and/or enhancing the function of GSK3ß. Therefore, ORI can be potentially used as an effective adjuvant agent for the clinical management of OS.

All-trans retinoic acid modulates bone morphogenic protein 9-induced osteogenesis and adipogenesis of preadipocytes through BMP/Smad and Wnt/ß-catenin signaling pathways.

It is known that excessive adipogenesis contributes to osteoporosis, suggesting that trans-differentiation of adipogenic committed preadipocytes into osteoblasts may be a potential therapeutical approach for osteoporosis. We explored whether bone morphogenic protein 9 (BMP9) could induce 3T3-L1 preadipocytes to trans-differentiate into osteoblasts. BMP9 effectively increased expression of osteogenic markers and promoted mineralization in preadipocytes. However, BMP9 also led to adipogenic differentiation of preadipocytes, as evidenced by increased lipid accumulation and up-regulation of adipogenic transcription factors. In order to regulate the switch between osetogenesis and adipogenesis, we evaluated the effect of all-trans retinoic acid (ATRA) on BMP9-induced differentiation of preadipocytes. We found that ATRA enhanced BMP9-induced osteogenic differentiation and blocked BMP9-induced adipogenic differentiation both in vitro and in vivo. Mechanistically, ATRA was shown to elevate BMP9 expression and activate BMP/Smad signaling. Additionally, BMP9 and ATRA exerted a synergistic effect on activation of Wnt/ß-catenin signaling. Knockdown of ß-catenin abolished the stimulatory effect of ATRA on BMP9-induced alkaline phosphatase activity and reversed the inhibitory effect of ATRA on BMP9-induced adipogenesis in preadipocytes. Furthermore, ATRA and BMP9 synergistically repressed glycogen synthase kinase 3ß (GSK3ß) activity and promoted Akt phosphorylation, and inhibited expression of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) that antagonizes phosphatidylinositol-3-kinase (PI3K) function, suggesting that Wnt/ß-catenin signaling was activated at least partly through PI3K/Akt/GSK3ß pathway. Collectively, ATRA mediated BMP9-induced osteogenic or adipogenic differentiation of 3T3-L1 preadipocytes by BMP/Smad and Wnt/ß-catenin signaling. The combination of BMP9 and ATRA may be explored as an effective therapeutic strategy for osteoporosis.

BMP9 and COX-2 form an important regulatory loop in BMP9-induced osteogenic differentiation of mesenchymal stem cells.

Mesenchymal stem cells (MSCs) can self-renew and differentiate into osteogenic, chondrogenic, adipogenic and myogenic lineages. It's reported that bone morphogenetic protein 9 (BMP9) is one of the most potent osteogenic BMPs to initiate the commitment of MSCs to osteoblast lineage. Cyclooxygenase-2 (COX-2) is critical for bone fracture healing and osteogenic differentiation in MSCs. However, the relationship between COX-2 and BMP9 in osteogenesis remains unknown. Herein, we investigate the role of COX-2 in BMP9-induced osteogenesis in MSCs. We demonstrate that COX-2 is up-regulated as a target of BMP9 in MSCs. Both COX-2 inhibitor (NS-398) and COX-2 knockdown siRNAs can effectively decrease alkaline phosphatase (ALP) activities induced by BMP9 in MSCs. NS-398 also down-regulates BMP9-induced expression of osteopontin and osteocalcin, so does the matrix mineralization. The in vivo studies indicate that knockdown of COX-2 attenuates BMP9-induced ectopic bone formation. In perinatal limb culture assay, NS-398 is shown to reduce the hypertropic chondrocyte zone and ossification induced by BMP9. Mechanistically, knockdown of COX-2 significantly inhibits the BMP9 up-regulated expression of Runx2 and Dlx-5 in MSCs, which can be rescued by exogenous expression of COX-2. Furthermore, knockdown of COX-2 apparently reduces BMP9 induced BMPR-Smad reporter activity, the phosphorylation of Smad1/5/8, and the expression of Smad6 and Smad7 in MSCs. NS-398 blocks the expression of BMP9 mediated by BMP9 recombinant adenovirus. Taken together, our findings suggest that COX-2 plays an important role in BMP9 induced osteogenic differentiation in MSCs; BMP9 and COX-2 may form an important regulatory loop to orchestrate the osteogenic differentiation in MSCs.

The effect of adenovirus-mediated siRNA targeting BMPR-II on UHMWPE-induced osteoclast formation.

Aseptic loosening (AL) is the single most common complication of total joint arthroplasty. The critical factor may contribute to loosening is the adverse tissue response to wear debris. A growing body of literature suggests that BMPs influence the formation and activity of osteoclasts, and BMP signaling plays an important role in the osteoclast formation. In this study, we have employed an RNA interference approach by transfecting a small interfering RNA (siRNA) specific for BMPR-II, to determine the possible importance of this receptor as a target for UHMWPE (Ultra high molecular weight polyethylene) induced osteoclastogenesis in the air pouch model in vivo. Meanwhile, in order to further elucidation of the mechanism of BMPR-II signaling pathway in osteoclast formation, we investigated the effects of siBMPR-II toward RANKL induced osteoclast differentiation in vitro. The present study showed that locally injection of adenovirus-mediated siRNA targeting BMPR-II appears to be a feasible and effective candidate to treat or prevent wear debris-associated osteolysis. Furthermore, we revealed that the effects of BMPR-II signaling on osteoclast formation are mediated directly by osteoclast itself, as well as indirectly by altered expression of RANKL and OPG in osteoblast.

Polarization information for terahertz imaging.

A method to analyze the change in the polarization state of a terahertz (THz) wave by using a typical electro-optic sampling setup with a ?110? zinc-blende crystal as a sensor is presented. To illustrate knowledge of the polarization of the THz pulse, the THz detection function in a ZnTe crystal is presented. Two kinds of Jones matrix for the birefringence device and the polarizer device are used to analyze the polarization change in the THz electric field caused by the sample. It is found that THz polarization imaging is sensitive to the edge of the sample.