{"title":"ATP6V1H facilitates osteogenic differentiation in MC3T3-E1 cells via Akt/GSK3β signaling pathway.","authors":"Fusong Jiang, Haojie Shan, Chenhao Pan, Zubin Zhou, Keze Cui, Yuanliang Chen, Haibo Zhong, Zhibin Lin, Nan Wang, Liang Yan, Xiaowei Yu","doi":"10.1080/15476278.2019.1633869","DOIUrl":"https://doi.org/10.1080/15476278.2019.1633869","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) accounts for approximately 90% of all diabetic patients, and osteoporosis is one of the complications during T2DM process. ATP6V1H (V-type proton ATPase subunit H) displays crucial roles in inhibiting bone loss, but its role in osteogenic differentiation remains unknown. Therefore in this study, we aimed to explore the biological role of ATP6V1H in osteogenic differentiation. OM (osteogenic medium) and HG (high glucose and free fatty acids) were used to induce the MC3T3-E1 cells into osteogenic differentiation in a T2DM simulating environment. CCK8 assay was used to detect cell viability. Alizarin Red staining was used to detect the influence of ATP6V1H on osteogenic differentiation. ATP6V1H expression increased in OM-MC3T3-E1 cells, while decreased in OM+HG-MC3T3-E1 cells. ATP6V1H promoted osteogenic differentiation of OM+HG-MC3T3-E1 cells. Overexpression of ATP6V1H inhibited Akt/GSK3β signaling pathway, while knockdown of ATP6V1H promoted Akt/GSK3β signaling pathway. ATP6V1H overexpression promoted osteogenic differentiation of OM+HG-MC3T3-E1 cells. The role of ATP6V1H in osteogenic differentiation in a T2DM simulating environment involved in Akt/GSK3β signaling pathway. These data demonstrated that ATP6V1H could serve as a potential target for osteogenic differentiation in a T2DM simulating environment.</p>","PeriodicalId":19596,"journal":{"name":"Organogenesis","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15476278.2019.1633869","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37130242","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 : 2018-01-02Epub Date: 2018-02-20DOI: 10.1080/15476278.2018.1436924
Jie Sun, Zhijing Wang, Xirui Wang
{"title":"Suppression of LRRC19 promotes cutaneous wound healing in pressure ulcers in mice.","authors":"Jie Sun, Zhijing Wang, Xirui Wang","doi":"10.1080/15476278.2018.1436924","DOIUrl":"https://doi.org/10.1080/15476278.2018.1436924","url":null,"abstract":"<p><p>The ischemia-reperfusion (I/R) induced skin lesion has been identified as primary cause of pressure ulcer. Better understanding of the mechanism is required for new therapy development. Leucine rich repeat containing protein 19 (LRRC19) is a recently discovered transmembrane protein containing leucine-rich repeats and plays a role in immune response. To investigate the role of LRRC19 in pressure ulcers, mouse ulcer model was established with two cycles of I/R. The expression of LRRC19 was assessed during injury. siRNA mediated LRRC19 downregulation was applied to investigate the disease severity, immune cell infiltration and pro-inflammatory cytokines production. The primary skin fibroblasts were stimulated with IL-1β to dissect the molecular mechanism. LRRC19 was readily induced in I/R induced lesion site in a pattern mimicking the disease progress as measured by wound area. Knockdown of LRRC19 by siRNA significantly alleviated the disease severity and attenuated immune cell infiltration and pro-inflammatory cytokines production. In primary skin fibroblast model, siRNA knockdown of LRRC19 suppressed IL-1β mediated NFκB activation and its downstream cytokines production. LRRC19 was a novel factor for I/R-induced tissue damage by promoting NFκB dependent pro-inflammatory response. Our results supported that LRRC19 could be a potential therapeutic target for pressure ulcers.</p>","PeriodicalId":19596,"journal":{"name":"Organogenesis","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2018-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15476278.2018.1436924","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35847320","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 : 2018-01-02Epub Date: 2018-02-15DOI: 10.1080/15476278.2017.1421882
Michael S Hu, Mimi R Borrelli, Wan Xing Hong, Samir Malhotra, Alexander T M Cheung, Ryan C Ransom, Robert C Rennert, Shane D Morrison, H Peter Lorenz, Michael T Longaker
{"title":"Embryonic skin development and repair.","authors":"Michael S Hu, Mimi R Borrelli, Wan Xing Hong, Samir Malhotra, Alexander T M Cheung, Ryan C Ransom, Robert C Rennert, Shane D Morrison, H Peter Lorenz, Michael T Longaker","doi":"10.1080/15476278.2017.1421882","DOIUrl":"10.1080/15476278.2017.1421882","url":null,"abstract":"<p><p>Fetal cutaneous wounds have the unique ability to completely regenerate wounded skin and heal without scarring. However, adult cutaneous wounds heal via a fibroproliferative response which results in the formation of a scar. Understanding the mechanism(s) of scarless wound healing leads to enormous clinical potential in facilitating an environment conducive to scarless healing in adult cutaneous wounds. This article reviews the embryonic development of the skin and outlines the structural and functional differences in adult and fetal wound healing phenotypes. A review of current developments made towards applying this clinical knowledge to promote scarless healing in adult wounds is addressed.</p>","PeriodicalId":19596,"journal":{"name":"Organogenesis","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2018-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150059/pdf/kogg-14-01-1421882.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35809515","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 : 2018-01-02DOI: 10.1080/15476278.2018.1455010
Hongpeng Yang, Yue Guo, Dawei Wang, Xiaofei Yang, Chengzhi Ha
{"title":"Effect of TAK1 on osteogenic differentiation of mesenchymal stem cells by regulating BMP-2 via Wnt/β-catenin and MAPK pathway.","authors":"Hongpeng Yang, Yue Guo, Dawei Wang, Xiaofei Yang, Chengzhi Ha","doi":"10.1080/15476278.2018.1455010","DOIUrl":"https://doi.org/10.1080/15476278.2018.1455010","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) have the ability to differentiate into osteoblasts and chondrocytes. In vitro osteogenic differentiation is critical but the molecular mechanism has yet to be further clarified. The role of TGF-β activated kinase 1 (TAK1) in MSCs osteogenesis differentiation has not been reported. By adding si-TAK1 and rhTAK1, the osteogenic differentiation of MSCs was measured. Expression levels of the osteoblastic marker genes during osteogenic differentiation of MSCs were checked. As well as molecules involved in BMP and Wnt/β-catenin signaling pathways. The phosphorylation of p38 and JNK was also checked. TAK1 is essential for mineralization of MSCs at low concentration, but excessive rhTAK1 inhibits mineralization of MSCs. It up regulates the expression levels of bone sialoprotein (BSP), osteocalcin (OSC), Alkaline phosphatase (ALP), and RUNX2 during osteogenic differentiation of MSCs. It can also promote TGF-β/BMP-2 gene expression and β-catenin expression, and down regulate GSK-3β expression. Meanwhile, TAK1 promotes the phosphorylation of p38 and JNK. Additionally, TAK1 up regulates the expression of BMP-2 at all concentration under the inhibition of p38 and JNK. Our results suggested that TAK1 is essential in MSCs osteogenesis differentiation, and functions as a double-edged sword, probably through regulation of β-catenin and p38/JNK.</p>","PeriodicalId":19596,"journal":{"name":"Organogenesis","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2018-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15476278.2018.1455010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40441366","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":"Effects of porcine acellular dermal matrix treatment on wound healing and scar formation: Role of Jag1 expression in epidermal stem cells.","authors":"Xiao-Dong Chen, Shu-Bin Ruan, Ze-Peng Lin, Ziheng Zhou, Feng-Gang Zhang, Rong-Hua Yang, Ju-Lin Xie","doi":"10.1080/15476278.2018.1436023","DOIUrl":"https://doi.org/10.1080/15476278.2018.1436023","url":null,"abstract":"<p><p>Skin wound healing involves Notch/Jagged1 signaling. However, little is known how Jag1 expression level in epidermal stem cells (ESCs) contributes to wound healing and scar formation. We applied multiple cellular and molecular techniques to examine how Jag1 expression in ESCs modulates ESCs differentiation to myofibroblasts (MFB) in vitro, interpret how Jag1 expression in ESCs is involved in wound healing and scar formation in mice, and evaluate the effects of porcine acellular dermal matrix (ADM) treatment on wound healing and scar formation. We found that Jag1, Notch1 and Hes1 expression was up-regulated in the wound tissue during the period of wound healing. Furthermore, Jag1 expression level in the ESCs was positively associated with the level of differentiation to MFB. ESC-specific knockout of Jag1 delayed wound healing and promoted scar formation in vivo. In addition, we reported that porcine ADM treatment after skin incision could accelerate wound closure and reduce scar formation in vivo. This effect was associated with decreased expression of MFB markers, including α-SMA Col-1 and Col-III in wound tissues. Finally, we confirmed that porcine ADM treatment could increase Jag1, Notch1 and Hesl expression in wound tissues. Taken together, our results suggested that ESC-specific Jag1 expression levels are critical for wound healing and scar formation, and porcine ADM treatment would be beneficial in promoting wound healing and preventing scar formation by enhancing Notch/Jagged1 signaling pathway in ESCs.</p>","PeriodicalId":19596,"journal":{"name":"Organogenesis","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2018-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15476278.2018.1436023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35810874","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 : 2018-01-02Epub Date: 2018-02-01DOI: 10.1080/15476278.2018.1423931
Yohan Kim, Kyojin Kang, Sangtae Yoon, Ji Sook Kim, Su A Park, Wan Doo Kim, Seung Bum Lee, Ki-Young Ryu, Jaemin Jeong, Dongho Choi
{"title":"Prolongation of liver-specific function for primary hepatocytes maintenance in 3D printed architectures.","authors":"Yohan Kim, Kyojin Kang, Sangtae Yoon, Ji Sook Kim, Su A Park, Wan Doo Kim, Seung Bum Lee, Ki-Young Ryu, Jaemin Jeong, Dongho Choi","doi":"10.1080/15476278.2018.1423931","DOIUrl":"https://doi.org/10.1080/15476278.2018.1423931","url":null,"abstract":"<p><p>Isolated primary hepatocytes from the liver are very similar to in vivo native liver hepatocytes, but they have the disadvantage of a limited lifespan in 2D culture. Although a sandwich culture and 3D organoids with mesenchymal stem cells (MSCs) as an attractive assistant cell source to extend lifespan can be used, it cannot fully reproduce the in vivo architecture. Moreover, long-term 3D culture leads to cell death because of hypoxic stress. Therefore, to overcome the drawback of 2D and 3D organoids, we try to use a 3D printing technique using alginate hydrogels with primary hepatocytes and MSCs. The viability of isolated hepatocytes was more than 90%, and the cells remained alive for 7 days without morphological changes in the 3D hepatic architecture with MSCs. Compared to a 2D system, the expression level of functional hepatic genes and proteins was higher for up to 7 days in the 3D hepatic architecture. These results suggest that both the 3D bio-printing technique and paracrine molecules secreted by MSCs supported long-term culture of hepatocytes without morphological changes. Thus, this technique allows for widespread expansion of cells while forming multicellular aggregates, may be applied to drug screening and could be an efficient method for developing an artificial liver.</p>","PeriodicalId":19596,"journal":{"name":"Organogenesis","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2018-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15476278.2018.1423931","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35759824","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 : 2018-01-01Epub Date: 2018-09-25DOI: 10.1080/15476278.2018.1517508
Srijan Tandukar, Sundaram Hariharan
{"title":"Xenotransplantation.","authors":"Srijan Tandukar, Sundaram Hariharan","doi":"10.1080/15476278.2018.1517508","DOIUrl":"https://doi.org/10.1080/15476278.2018.1517508","url":null,"abstract":"<p><p>The transplantation of living cells, tissues or organs from one species to another is termed xenotransplantation. The history of xenotransplantation is as old as allogeneic transplantation itself. Early attempts were made at a time when the immunologic basis of organ rejection were poorly understood. The advent of potent immunosuppressive medications along with the parallel advances in the field of genetic engineering has provided a fresh perspective on the role of xenotransplantation as a means to alleviate the disparity between the number of candidates on the waitlist and the available organs. As the science behind xenotransplantation advances, the transplantation community must take it upon themselves to educate the community at large regarding both the benefits and potential risks of this promising field.</p>","PeriodicalId":19596,"journal":{"name":"Organogenesis","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15476278.2018.1517508","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36521169","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 : 2018-01-01Epub Date: 2018-10-05DOI: 10.1080/15476278.2018.1517564
Corey Eymard, James Markmann
{"title":"Normothermic ex vivo liver perfusion: platform for liver graft assessment and therapeutic modification.","authors":"Corey Eymard, James Markmann","doi":"10.1080/15476278.2018.1517564","DOIUrl":"https://doi.org/10.1080/15476278.2018.1517564","url":null,"abstract":"<p><p>Liver transplantation as a treatment for end stage liver failure remains limited in the United States by the number and quality of donor allografts. Static cold storage, the current standard of care for organ storage prior to transplantation, offers no method for assessment or therapeutic modification. Cold ischemia and its attendant hypoxia deplete cellular adenosine triphosphate (ATP) stores, promote cellular damage, and degrade overall organ quality. Normothermic ex vivo liver perfusion (NEVLP) offers the potential for assessment of allograft function and restoration of intracellular energy stores prior to transplantation. A completed phase III randomized trial demonstrated livers undergoing NEVLP prior to transplantation demonstrate superior early graft function and less early graft dysfunction. NEVLP offers a platform for modification of the allograft via the application of defatting or therapeutic cocktails, missense RNA technology, or gene editing modalities. The wide versatility of NEVLP appears to be a promising tool to expand the current pool of transplantable liver allografts.</p>","PeriodicalId":19596,"journal":{"name":"Organogenesis","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15476278.2018.1517564","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36560284","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}