OrganogenesisPub Date : 2017-07-03Epub Date: 2017-06-09DOI: 10.1080/15476278.2017.1329789
Yannan Zhao, Zhifeng Xiao, Bing Chen, Jianwu Dai
{"title":"The neuronal differentiation microenvironment is essential for spinal cord injury repair.","authors":"Yannan Zhao, Zhifeng Xiao, Bing Chen, Jianwu Dai","doi":"10.1080/15476278.2017.1329789","DOIUrl":"https://doi.org/10.1080/15476278.2017.1329789","url":null,"abstract":"<p><p>Spinal cord injury (SCI) often leads to substantial disability due to loss of motor function and sensation below the lesion. Neural stem cells (NSCs) are a promising strategy for SCI repair. However, NSCs rarely differentiate into neurons; they mostly differentiate into astrocytes because of the adverse microenvironment present after SCI. We have shown that myelin-associated inhibitors (MAIs) inhibited neuronal differentiation of NSCs. Given that MAIs activate epidermal growth factor receptor (EGFR) signaling, we used a collagen scaffold-tethered anti-EGFR antibody to attenuate the inhibitory effects of MAIs and create a neuronal differentiation microenvironment for SCI repair. The collagen scaffold modified with anti-EGFR antibody prevented the inhibition of NSC neuronal differentiation by myelin. After transplantation into completely transected SCI animals, the scaffold-linked antibodies induced production of nascent neurons from endogenous and transplanted NSCs, which rebuilt the neuronal relay by forming connections with each other or host neurons to transmit electrophysiological signals and promote functional recovery. Thus, a scaffold-based strategy for rebuilding the neuronal differentiation microenvironment could be useful for SCI repair.</p>","PeriodicalId":19596,"journal":{"name":"Organogenesis","volume":"13 3","pages":"63-70"},"PeriodicalIF":2.3,"publicationDate":"2017-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15476278.2017.1329789","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35075995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OrganogenesisPub Date : 2017-07-03Epub Date: 2017-06-09DOI: 10.1080/15476278.2017.1332554
Xi Lu, Fang Yu, Junjun Liu, Wenping Cai, Yumei Zhao, Shouliang Zhao, Shangfeng Liu
{"title":"The epidemiology of supernumerary teeth and the associated molecular mechanism.","authors":"Xi Lu, Fang Yu, Junjun Liu, Wenping Cai, Yumei Zhao, Shouliang Zhao, Shangfeng Liu","doi":"10.1080/15476278.2017.1332554","DOIUrl":"https://doi.org/10.1080/15476278.2017.1332554","url":null,"abstract":"<p><p>Supernumerary teeth are common clinical dental anomalies. Although various studies have provided abundant information regarding genes and signaling pathways involved in tooth morphogenesis, which include Wnt, FGF, BMP, and Shh, the molecular mechanism of tooth formation, especially for supernumerary teeth, is still unclear. In the population, some cases of supernumerary teeth are sporadic, while others are syndrome-related with familial hereditary. The prompt and accurate diagnosis of syndrome related supernumerary teeth is quite important for some distinctive disorders. Mice are the most commonly used model system for investigating supernumerary teeth. The upregulation of Wnt and Shh signaling in the dental epithelium results in the formation of multiple supernumerary teeth in mice. Understanding the molecular mechanism of supernumerary teeth is also a component of understanding tooth formation in general and provides clinical guidance for early diagnosis and treatment in the future.</p>","PeriodicalId":19596,"journal":{"name":"Organogenesis","volume":"13 3","pages":"71-82"},"PeriodicalIF":2.3,"publicationDate":"2017-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15476278.2017.1332554","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35073790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OrganogenesisPub Date : 2017-07-03Epub Date: 2017-05-26DOI: 10.1080/15476278.2017.1322243
Yang Wang, Kazuki Takeishi, Zhao Li, Eduardo Cervantes-Alvarez, Alexandra Collin de l'Hortet, Jorge Guzman-Lepe, Xiao Cui, Jiye Zhu
{"title":"Microenvironment of a tumor-organoid system enhances hepatocellular carcinoma malignancy-related hallmarks.","authors":"Yang Wang, Kazuki Takeishi, Zhao Li, Eduardo Cervantes-Alvarez, Alexandra Collin de l'Hortet, Jorge Guzman-Lepe, Xiao Cui, Jiye Zhu","doi":"10.1080/15476278.2017.1322243","DOIUrl":"https://doi.org/10.1080/15476278.2017.1322243","url":null,"abstract":"<p><p>Organ-like microenviroment and 3-dimensional (3D) cell culture conformations have been suggested as promising approaches to mimic in a micro-scale a whole organ cellular functions and interactions present in vivo. We have used this approach to examine biologic features of hepatocellular carcinoma (HCC) cells. In this study, we demonstrate that hepatocellular carcinoma (HCC) cells, fibroblasts, endothelial cells and extracellular matrix can generate organoid-like spheroids that enhanced numerous features of human HCC observed in vivo. We show that the addition of non-parenchymal cells such as fibroblast and endothelial cells is required for spheroid formation as well as the maintenance of the tissue-like structure. Furthermore, HCC cells cultured as spheroids with non-parenchymal cells express more neo-angiogenesis-related markers (VEGFR2, VEGF, HIF-α), tumor-related inflammatory factors (CXCR4, CXCL12, TNF-α) and molecules-related to induced epithelial-mesenchymal transition (TGFβ, Vimentin, MMP9) compared with organoids containing only HCC cells. These results demonstrate the importance of non-parenchymal cells in the cellular composition of HCC organoids. The novelty of the multicellular-based organotypic culture system strongly supports the integration of this approach in a high throughput approach to identified patient-specific HCC malignancy and accurate anti-tumor therapy screening after surgery.</p>","PeriodicalId":19596,"journal":{"name":"Organogenesis","volume":"13 3","pages":"83-94"},"PeriodicalIF":2.3,"publicationDate":"2017-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15476278.2017.1322243","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35033188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OrganogenesisPub Date : 2017-07-03Epub Date: 2017-06-09DOI: 10.1080/15476278.2017.1331196
Guang Li, Jing Hu, Hui Chen, Liang Chen, Na Zhang, Lisheng Zhao, Ning Wen, Yongjin Yang
{"title":"Enamel matrix derivative enhances the proliferation and osteogenic differentiation of human periodontal ligament stem cells on the titanium implant surface.","authors":"Guang Li, Jing Hu, Hui Chen, Liang Chen, Na Zhang, Lisheng Zhao, Ning Wen, Yongjin Yang","doi":"10.1080/15476278.2017.1331196","DOIUrl":"https://doi.org/10.1080/15476278.2017.1331196","url":null,"abstract":"<p><p>Periodontal ligament stem cells (PDLSCs) have mesenchymal-stem-cells-like qualities, and are considered as one of the candidates of future clinical application in periodontal regeneration therapy. Enamel matrix derivative (EMD) is widely used in promoting periodontal regeneration. However, the effects of EMD on the proliferation and osteogenic differentiation of human PDLSCs grown on the Ti implant surface are still no clear. Therefore, this study examined the effects of EMD on human PDLSCs in vitro. Human PDLSCs were isolated from healthy participants, and seeded on the surface of Ti implant disks and stimulated with various concentrations of EMD. Cell proliferation was determined with Cell Counting Kit-8 (CCK-8). The osteogenic differentiation of PDLSCs was evaluated by the measurement of alkaline phosphatase (ALP) activity, Alizarin red staining, and real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. The results indicated that EMD at concentrations (5-60 µg/ml) increased the viability and proliferation of PDLSCs. The treatment with 30 and 60 µg/ml of EMD significantly elevated ALP activity, augmented mineralized nodule formation and calcium deposition, and upregulated the mRNA and protein levels of Runx-2 and osteocalcin (OCN) in the PDLSCs grown on the Ti surface. Further investigation found that EMD treatment did not change the protein levels of phosphatidylinositol-3-kinase (PI3K), p-PI3K, Akt and mTOR, but significantly upregulated the phosphorylated levels of Akt and mTOR. Collectively, these results suggest that EMD stimulation can promote the proliferation and osteogenic differentiation of PDLSCs grown on Ti surface, which is possibly associated with the activation of Akt/mTOR signaling pathway.</p>","PeriodicalId":19596,"journal":{"name":"Organogenesis","volume":"13 3","pages":"103-113"},"PeriodicalIF":2.3,"publicationDate":"2017-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15476278.2017.1331196","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35074875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OrganogenesisPub Date : 2017-04-03Epub Date: 2017-02-23DOI: 10.1080/15476278.2017.1295904
Kelvin K L Wong, Lauren C Y Tang, Jerry Zhou, Vincent Ho
{"title":"Analysis of spatiotemporal pattern and quantification of gastrointestinal slow waves caused by anticholinergic drugs.","authors":"Kelvin K L Wong, Lauren C Y Tang, Jerry Zhou, Vincent Ho","doi":"10.1080/15476278.2017.1295904","DOIUrl":"https://doi.org/10.1080/15476278.2017.1295904","url":null,"abstract":"<p><p>Anticholinergic drugs are well-known to cause adverse effects, such as constipation, but their effects on baseline contractile activity in the gut driven by slow waves is not well established. In a video-based gastrointestinal motility monitoring (GIMM) system, a mouse's small intestine was placed in Krebs solution and recorded using a high definition camera. Untreated controls were recorded for each specimen, then treated with a therapeutic concentration of the drug, and finally, treated with a supratherapeutic dose of the drug. Next, the video clips showing gastrointestinal motility were processed, giving us the segmentation motions of the intestine, which were then converted via Fast Fourier Transform (FFT) into their respective frequency spectrums. These contraction quantifications were analyzed from the video recordings under standardised conditions to evaluate the effect of drugs. Six experimental trials were included with benztropine and promethazine treatments. Only the supratherapeutic dose of benztropine was shown to significantly decrease the amplitude of contractions; at therapeutic doses of both drugs, neither frequency nor amplitude was significantly affected. We have demonstrated that intestinal slow waves can be analyzed based on the colonic frequency or amplitude at a supratherapeutic dose of the anticholinergic medications. More research is required on the effects of anticholinergic drugs on these slow waves to ascertain the true role of ICC in neurologic control of gastrointestinal motility.</p>","PeriodicalId":19596,"journal":{"name":"Organogenesis","volume":"13 2","pages":"39-62"},"PeriodicalIF":2.3,"publicationDate":"2017-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15476278.2017.1295904","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34798478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OrganogenesisPub Date : 2017-01-19DOI: 10.1080/15476278.2017.1280211
Yasuhito Sekimoto, H. Obara, K. Matsubara, N. Fujimura, H. Harada, Y. Kitagawa
{"title":"Comparison of early vascular morphological changes between bioresorbable poly-L-lactic acid scaffolds and metallic stents in porcine iliac arteries","authors":"Yasuhito Sekimoto, H. Obara, K. Matsubara, N. Fujimura, H. Harada, Y. Kitagawa","doi":"10.1080/15476278.2017.1280211","DOIUrl":"https://doi.org/10.1080/15476278.2017.1280211","url":null,"abstract":"ABSTRACT Bioresorbable scaffolds have the potential to overcome several problems associated with metallic stents. Bioresorbable poly-L-lactic acid (PLLA) scaffold implantation for the treatment of peripheral artery disease has already been reported in animal models and clinical trials; however, no studies comparing PLLA scaffolds and bare metal stents (BMSs) with regard to early vascular morphological changes, identified using intravascular ultrasound (IVUS) analysis, have been reported. In this study, PLLA scaffolds and BMSs were implanted bilaterally in iliac arteries of five miniature pigs. Digital subtraction angiography and IVUS were performed before and immediately after stent implantation and at 6-week follow-up. All PLLA scaffolds and BMSs were patent at 6-week follow-up. Per IVUS analysis, the percent area stenosis did not significantly differ between PLLA scaffolds and BMSs (65.7% vs. 67.2%, P = .761). Furthermore, percent vessel lumen change also did not differ significantly. Neointima formation (the neointimal area plus medial area) was significantly less with PLLA scaffolds than with BMSs (15.65 mm2 vs. 25.69 mm2, P < .001). In conclusion, based on IVUS results, short-term results after stent implantation in porcine iliac arteries were comparable between PLLA scaffolds and BMSs. Therefore, PLLA scaffolds are safe and feasible for implantation in peripheral arteries.","PeriodicalId":19596,"journal":{"name":"Organogenesis","volume":"13 1","pages":"29 - 38"},"PeriodicalIF":2.3,"publicationDate":"2017-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15476278.2017.1280211","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43698128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OrganogenesisPub Date : 2017-01-02DOI: 10.1080/15476278.2016.1278133
Eduardo Cervantes-Alvarez, Yang Wang, Alexandra Collin de l'Hortet, J. Guzman‐Lepe, Jiye Zhu, K. Takeishi
{"title":"Current strategies to generate mature human induced pluripotent stem cells derived cholangiocytes and future applications","authors":"Eduardo Cervantes-Alvarez, Yang Wang, Alexandra Collin de l'Hortet, J. Guzman‐Lepe, Jiye Zhu, K. Takeishi","doi":"10.1080/15476278.2016.1278133","DOIUrl":"https://doi.org/10.1080/15476278.2016.1278133","url":null,"abstract":"ABSTRACT Stem cell research has significantly evolved over the last few years, allowing the differentiation of pluripotent cells into almost any kind of lineage possible. Studies that focus on the liver have considerably taken a leap into this novel technology, and hepatocyte-like cells are being generated that are close to resembling actual hepatocytes both genotypically and phenotypically. The potential of this extends from disease models to bioengineering, and even also innovative therapies for end-stage liver disease. Nonetheless, too few attention has been given to the non-parenchymal cells which are also fundamental for normal liver function. This includes cholangiocytes, the cells of the biliary epithelium, without whose role in bile modification and metabolism would impair hepatocyte survival. Such can be observed in diseases that target them, so called cholangiopathies, for which there is much yet to study so as to improve therapeutical options. Protocols that describe the induction of human induced pluripotent stem cells into cholangiocytes are scarce, although progress is being achieved in this area as well. In order to give the current view on this emerging research field, and in hopes to motivate further advances, we present here a review on the known differentiation strategies with sight into future applications.","PeriodicalId":19596,"journal":{"name":"Organogenesis","volume":"13 1","pages":"1 - 15"},"PeriodicalIF":2.3,"publicationDate":"2017-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15476278.2016.1278133","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45020477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OrganogenesisPub Date : 2017-01-02DOI: 10.1080/15476278.2016.1276146
Wessam S. Hassanein, M. Uluer, John T. Langford, J. Woodall, A. Cimeno, U. Dhru, Avraham Werdesheim, Joshua Harrison, Carlos Rivera-Pratt, Stephen Klepfer, A. Khalifeh, Bryan Buckingham, P. Brazio, D. Parsell, Charlie Klassen, C. Drachenberg, R. Barth, J. LaMattina
{"title":"Recellularization via the bile duct supports functional allogenic and xenogenic cell growth on a decellularized rat liver scaffold","authors":"Wessam S. Hassanein, M. Uluer, John T. Langford, J. Woodall, A. Cimeno, U. Dhru, Avraham Werdesheim, Joshua Harrison, Carlos Rivera-Pratt, Stephen Klepfer, A. Khalifeh, Bryan Buckingham, P. Brazio, D. Parsell, Charlie Klassen, C. Drachenberg, R. Barth, J. LaMattina","doi":"10.1080/15476278.2016.1276146","DOIUrl":"https://doi.org/10.1080/15476278.2016.1276146","url":null,"abstract":"ABSTRACT Recent years have seen a proliferation of methods leading to successful organ decellularization. In this experiment we examine the feasibility of a decellularized liver construct to support growth of functional multilineage cells. Bio-chamber systems were used to perfuse adult rat livers with 0.1% SDS for 24 hours yielding decellularized liver scaffolds. Initially, we recellularized liver scaffolds using a human tumor cell line (HepG2, introduced via the bile duct). Subsequent studies were performed using either human tumor cells co-cultured with human umbilical vein endothelial cells (HUVECs, introduced via the portal vein) or rat neonatal cell slurry (introduced via the bile duct). Bio-chambers were used to circulate oxygenated growth medium via the portal vein at 37C for 5-7 days. Human HepG2 cells grew readily on the scaffold (n = 20). HepG2 cells co-cultured with HUVECs demonstrated viable human endothelial lining with concurrent hepatocyte growth (n = 10). In the series of neonatal cell slurry infusion (n = 10), distinct foci of neonatal hepatocytes were observed to repopulate the parenchyma of the scaffold. The presence of cholangiocytes was verified by CK-7 positivity. Quantitative albumin measurement from the grafts showed increasing albumin levels after seven days of perfusion. Graft albumin production was higher than that observed in traditional cell culture. This data shows that rat liver scaffolds support human cell ingrowth. The scaffold likewise supported the engraftment and survival of neonatal rat liver cell slurry. Recellularization of liver scaffolds thus presents a promising model for functional liver engineering.","PeriodicalId":19596,"journal":{"name":"Organogenesis","volume":"13 1","pages":"16 - 27"},"PeriodicalIF":2.3,"publicationDate":"2017-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15476278.2016.1276146","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44922098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OrganogenesisPub Date : 2016-10-01Epub Date: 2016-11-14DOI: 10.1080/15476278.2016.1252887
Elise M Gervais, Sharon J Sequeira, Weihao Wang, Stanley Abraham, Janice H Kim, Daniel Leonard, Kara A DeSantis, Melinda Larsen
{"title":"Par-1b is required for morphogenesis and differentiation of myoepithelial cells during salivary gland development.","authors":"Elise M Gervais, Sharon J Sequeira, Weihao Wang, Stanley Abraham, Janice H Kim, Daniel Leonard, Kara A DeSantis, Melinda Larsen","doi":"10.1080/15476278.2016.1252887","DOIUrl":"10.1080/15476278.2016.1252887","url":null,"abstract":"<p><p>The salivary epithelium initiates as a solid mass of epithelial cells that are organized into a primary bud that undergoes morphogenesis and differentiation to yield bilayered acini consisting of interior secretory acinar cells that are surrounded by contractile myoepithelial cells in mature salivary glands. How the primary bud transitions into acini has not been previously documented. We document here that the outer epithelial cells subsequently undergo a vertical compression as they express smooth muscle α-actin and differentiate into myoepithelial cells. The outermost layer of polarized epithelial cells assemble and organize the basal deposition of basement membrane, which requires basal positioning of the polarity protein, Par-1b. Whether Par-1b is required for the vertical compression and differentiation of the myoepithelial cells is unknown. Following manipulation of Par-1b in salivary gland organ explants, Par-1b-inhibited explants showed both a reduced vertical compression of differentiating myoepithelial cells and reduced levels of smooth muscle α-actin. Rac1 knockdown and inhibition of Rac GTPase function also inhibited branching morphogenesis. Since Rac regulates cellular morphology, we investigated a contribution for Rac in myoepithelial cell differentiation. Inhibition of Rac GTPase activity showed a similar reduction in vertical compression and smooth muscle α-actin levels while decreasing the levels of Par-1b protein and altering its basal localization in the outer cells. Inhibition of ROCK, which is required for basal positioning of Par-1b, resulted in mislocalization of Par-1b and loss of vertical cellular compression, but did not significantly alter levels of smooth muscle α-actin in these cells. Overexpression of Par-1b in the presence of Rac inhibition restored basement membrane protein levels and localization. Our results indicate that the basal localization of Par-1b in the outer epithelial cells is required for myoepithelial cell compression, and Par-1b is required for myoepithelial differentiation, regardless of its localization.</p>","PeriodicalId":19596,"journal":{"name":"Organogenesis","volume":"12 1","pages":"194-216"},"PeriodicalIF":2.3,"publicationDate":"2016-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5198941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"59981533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"IL-7 suppresses osteogenic differentiation of periodontal ligament stem cells through inactivation of mitogen-activated protein kinase pathway.","authors":"Cong-Xiang Jian, Quan-Shui Fan, Yong-He Hu, Yong He, Ming-Zhe Li, Wei-Yin Zheng, Yu Ren, Chen-Jun Li","doi":"10.1080/15476278.2016.1229726","DOIUrl":"https://doi.org/10.1080/15476278.2016.1229726","url":null,"abstract":"<p><p>Periodontal ligament stem cells (PDLSCs) are tissue-specific mesenchymal stem cells (MSCs), having an important role in regenerative therapy for teeth loss. Interleukin-7 (IL-7) is a key cytokine produced by stromal cells including MSCs, and exhibits specific roles for B and T cell development and osteoblasts differentiation of multiple myeloma. However, the effect of IL-7 on osteogenic differentiation of PDLSCs remains unclear. Therefore, in the present study we determined whether IL-7 affects the proliferation and osteogenic differentiation of PDLSCs in vitro and explored the associated signaling pathways for IL-7-mediated cell differentiation. The results demonstrated that the isolated human PDLSCs possessed MSCs features, highly expressing CD90, CD44, CD105, CD29 and CD73, and almost did not expressed CD34, CD45, CD11b, CD14 and CD117. IL-7 could not significantly affect the proliferation of PDLSCs, but it decreased their osteogenic differentiation and inhibited alkaline phosphatase (ALP) activity. The results of quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting exhibited that the expression levels of Runx-2, SP7 and osteocalcin (OCN) were significantly reduced by IL-7. Further studies indicated that IL-7 did not significantly change JNK, ERK1/2 and p38 protein production, but markedly suppressed their phosphorylation levels. These data suggest that IL-7 inhibits the osteogenic differentiation of PDLSCs probably via inactivation of mitogen-activated protein kinase (MAPK) signaling pathway.</p>","PeriodicalId":19596,"journal":{"name":"Organogenesis","volume":"12 4","pages":"183-193"},"PeriodicalIF":2.3,"publicationDate":"2016-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15476278.2016.1229726","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34350268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}