Cells Tissues Organs最新文献

{"title":"CCP1 loss in bone marrow mesenchymal stem cells inhibited osteogenic differentiation by enhancing microtubule glutamylation.","authors":"Cancan Pan, Xuyan Gong, Xuekui Wang, Huiyuan Wu, Yao Sun","doi":"10.1159/000546259","DOIUrl":"https://doi.org/10.1159/000546259","url":null,"abstract":"<p><p>Cytosolic carboxypeptidase 1 (CCP1) is a deglutamylase that antagonizes polyglutamylation. Mutations in human CCP1 gene cause a severe disease known as childhood-onset neurodegeneration with cerebellar atrophy (CONDCA), which is characterized by marked growth retardation. However, the role and mechanisms of CCP1 in skeletal development remain unclear. In this study, we used CCP1 knockout (CCP1-KO) mice to assess bone mass changes by micro-CT, HE, alkaline phosphatase (ALP) staining, tartrateresistant acid phosphatase (TRAP) staining and immunofluorescence staining. Changes in osteogenic differentiation, proliferation and migration capacity of bone marrow mesenchymal stem cells (BMSCs) were assessed by ALP, alizarin red (ARS) staining, quantitative real-time PCR (qRT-PCR), EdU staining and cell scratching assay. Then, tubulin glutamylation and primary cilia of BMSCs after deletion of CCP1 was analyzed by western blot (WB) and immunofluorescence staining. Finally, CB839, an inhibitor of glutamine metabolism, was used to detect changes in the osteogenic differentiation ability and primary cilia of BMSCs after reducing the elevated glutamylation level. CCP1-KO mice exhibited phenotypes relevant to humans, including reduced body size, decreased bone mass, and reduced bone density during growth and development. CCP1 deficiency impairs the proliferation, migration and osteogenic differentiation of BMSCs. Meanwhile, the number of pre-osteoblasts derived from BMSCs is decreased, leading to impaired osteogenesis. At the cellular level, CCP1 loss results in aberrant tubulin glutamylation, increased microtubule glutamylation, and shortened primary cilia in BMSCs. Finally, reduction of abnormally elevated tubulin glutamylation was efficacious for promoting osteogenic differentiation of BMSCs and restoring primary cilia length of BMSCs. We propose that CCP1 plays a critical role in regulating BMSCs differentiation and promotes osteogenesis by modulating the post-translational modifications (PTM) of tubulin, with a view to provide new targets for the prevention and treatment of hard tissue diseases.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-23"},"PeriodicalIF":2.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987015","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}

{"title":"Down regulation of Endo-beta-N-acetylglucosaminidase in Caenorhabditis elegans improves stress adaptivity.","authors":"Xinrong Lu, Yongliang Tong, Mengting Wu, Shaoxian Lyu, Jiale Fan, Junyu Zheng, Lin Zou, Danfeng Shen, Lin Rao, Linlin Hou, Cuiying Chen, Xunjia Cheng, Guiqin Sun, Zhiyong Shao, Li Chen","doi":"10.1159/000546244","DOIUrl":"https://doi.org/10.1159/000546244","url":null,"abstract":"<p><strong>Introduction: </strong>Endo-beta-N-acetylglucosaminidase (ENGASE) is one of the key enzymes involved in the structural and functional regulations of glycoproteins. Although its enzymatic activities and applications have been well studied in vitro, its biological function in vivo yet remains to be illustrated. In this study, the biological function of ENGASE in Caenorhabditis elegans (C. elegans) was explored in detail.</p><p><strong>Methods: </strong>An Engase gene knockout in C. elegans (CeEng-1 or CeEngase) was constructed and subjected to a panel of phenotypical and glycomics analysis. In addition, in vitro and in vivo ENGASE inhibition assays were performed.</p><p><strong>Results: </strong>Engase knockout worm's adaptivity to environmental stresses (heat and osmotic) was significantly improved, and its longevity was also increased mildly. A clustered change in basement membrane proteins (e.g., LAM-1, LAM-2, and EPI-1) was illustrated by Nglycopeptide analysis, suggesting ENGASE is involved in a basement membrane-based stress regulation. Then, the heat stress phenotype was further supported by in vivo CeEngase knockdown assay and in vitro and in vivo small compound inhibitory assay of CeENGASE, indicating ENGASE is a potential drug target for stress management.</p><p><strong>Conclusion: </strong>Engase is actively involved in a basement membrane-mediated stress adaptation, and could serve as a potential target for healthcare products.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-23"},"PeriodicalIF":2.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967018","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}

{"title":"Erratum.","authors":"","doi":"10.1159/000545551","DOIUrl":"https://doi.org/10.1159/000545551","url":null,"abstract":"","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983854","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":"Endocytotic Albumin Uptake Pathways in Human Adipose Stem Cells and Connection to Intracellular Calcium Oscillations and the Neonatal Fc receptor (FcRn).","authors":"Md Tanvir Morshed, Anne Bernhardt, Maria Wartenberg, Heinrich Sauer","doi":"10.1159/000545773","DOIUrl":"https://doi.org/10.1159/000545773","url":null,"abstract":"<p><p>Intracellular Ca2+ oscillations of unknown function occur in human adipose tissue stem cells (ASCs). In the present study we investigated whether Ca2+ oscillations in ASCs from subcutaneous fat tissue derived from female patients were driving albumin endocytosis by involving the neonatal Fc receptor (FcRn), which is mediating the recycling of albumin and IgG. Our data demonstrated that endocytosis of albumin occurred by micropinocytosis (inhibition by cytochalasin D, wortmannin, and ethylisopropylamiloride (EIPA)), caveolae-dependent (inhibition by genistein and nystatin) and clathrin-mediated (inhibition by Dyngo-4a) pathways. In serum-free medium Ca2+ oscillations were absent, but could be induced by addition of either fetal bovine serum (FBS), albumin, IgG or a stimulating antibody against FcRn. Consequently, FcRn expression was demonstrated in ASCs by western blot analysis and immunohistochemistry, and colocalized with fluorescence-labelled, endocytosed albumin. Ca2+ oscillations were inhibited by the Ca2+ chelating agent BAPTA, the store-operated Ca2+ entry (SOCE) inhibitor SKF96365, the Ca2+ sensing receptor (CaSR) inhibitor NPS-2143, the macropinocytosis inhibitors cytochalasin D, wortmannin, and EIPA, the caveolae-dependent endocytosis inhibitors genistein and nystatin, and the clathrin-mediated endocytosis inhibitor Dyngo-4a. Uptake of fluorescence-labelled albumin was inhibited by agents interfering with Ca2+ oscillations and endocytosis blockers. Notably, not only intracellular albumin and IgG accumulation, but also Ca2+ oscillations were inhibited by the FcRn-blocking antibody nipocalimab which interferes with the IgG binding site of FcRn. Moreover, siRNA-mediated downregulation of FcRn protein expression significantly reduced intracellular albumin content, the number of cells displaying Ca2+ oscillations, and the duration and amplitude of Ca2+ signals. In summary, our data suggest that Ca2+ oscillations in human ASCs regulate albumin uptake and presumably IgG recycling via FcRn.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-29"},"PeriodicalIF":2.9,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981878","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}

{"title":"Superior Mesenteric Artery during Intestinal Loop Formation and Its Positional Changes from the Extracoelom to the Abdominal Cavity.","authors":"Tetsuya Takakuwa, Maki Kakeya, Nanase Ishida, Toru Kanahashi, Sena Fujii, Jörg Männer, Shigehito Yamada","doi":"10.1159/000545751","DOIUrl":"10.1159/000545751","url":null,"abstract":"<p><strong>Introduction: </strong>Features of the superior mesenteric artery (SMA) and its intestinal branches during the embryonic and early fetal periods have not been fully described. We aimed to comprehensively elucidate the characteristics of intestinal branch artery formation in the SMA.</p><p><strong>Methods: </strong>Serial tissue sections of seven early fetal specimens belonging to the Blechschmidt collection were digitalized and used for segmentation and reconstruction of the intestinal loop, SMA trunk, intestinal branch arteries, and mesentery for further analysis.</p><p><strong>Results: </strong>The intestinal branch arteries fed the intestinal tract from the oral side to the anal side, according to the order of their origin from the root to the periphery of the SMA trunk. SMA and intestinal branches were not as strongly conserved in their morphology as indicated in previous research but varied between specimens. Most intestinal branch arteries exhibited frequent branching with small intervals at the periphery, whereas the proximal branch exhibited few branches. Only a few peripheral branches made contact with the neighboring intestinal branch arteries. The fetal intestinal branch artery architecture differed greatly from that of adults. There were considerable inter- and intra-specimen variations in the intestinal tract length per feeding intestinal branch artery. The SMA branching arteries did not always supply each tertiary loop individually, and not every loop is connected to one branching artery.</p><p><strong>Conclusion: </strong>This study elucidates the characteristics of forming the SMA intestinal branch arteries. Specifically, the findings suggest that the SMA is similar to other arteries in that its branches show a level of variability in feeding tissues.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-12"},"PeriodicalIF":2.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810468","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":"Erratum.","authors":"","doi":"10.1159/000544895","DOIUrl":"10.1159/000544895","url":null,"abstract":"","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1"},"PeriodicalIF":2.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779083","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}

{"title":"Anatomy, Histology, Aetiology, Development and Functions of Cartilago Cordis: A Systematic Review.","authors":"Valentina Kubale, Adam Best, Shirley Mai, Thalia Smale, Aziza Alibhai, William Perez, Samir A A El-Gendy, Mohamed A M Alsafy, Craig J Sturrock, Catrin Sian Rutland","doi":"10.1159/000544776","DOIUrl":"https://doi.org/10.1159/000544776","url":null,"abstract":"<p><strong>Introduction: </strong>The cartilago cordis is a structure present within the cardiac skeleton of some, but not all, vertebrate species. This systematic review compared the presence, structure, and function of the cartilago cordis from published works covering all vertebrate species.</p><p><strong>Methods: </strong>Literature searches were conducted to obtain information relating to the anatomical location, morphology, prevalence, number of structures, development, and function.</p><p><strong>Results: </strong>The cartilago cordis was most commonly composed of hyaline cartilage but its location within the cardiac skeleton, anatomical, and histological structure varied between species. The cartilago cordis has not been documented in every vertebrate species, or every individual within each species, but it is present in 68 vertebrates including an amphibian, and some mammals, reptiles, and birds. The function of the cartilago cordis is unknown, but theories have ranged from an adaptive mechanism to support cardiac tissue through to roles in conduction and contraction, especially in areas of high mechanical stress. Possible links between the presence of a cartilago cordis and cardiac pathologies were also identified.</p><p><strong>Conclusion: </strong>The cartilago cordis varied in prevalence, structure, and location; further research is required to understand the function and development. In addition, it is possible there are more vertebrate species containing cartilago cordis than presently known about given its varying prevalence and sometimes small size.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-25"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762971","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}

{"title":"Updating the Role of JUNO and Factors Involved in Its Function during Fertilization.","authors":"Lucía Díaz-Fuster, Paula Sáez-Espinosa, Isabel Moya, Irene Peinado, María José Gómez-Torres","doi":"10.1159/000545000","DOIUrl":"https://doi.org/10.1159/000545000","url":null,"abstract":"<p><strong>Introduction: </strong>The final step of the fertilization process involves gametes adhesion and fusion. JUNO is an essential folate receptor 4 protein present in the ooplasm of oocytes, which binds to IZUMO1, its receptor on the sperm surface. Both proteins are indispensable for the sperm-oocyte interaction, and their absence results in infertility. Despite the importance of JUNO in reproduction, there is still controversy about how different factors affect the functionality of JUNO. Therefore, the goal of this study was to provide a comprehensive overview of what we know so far about the presence and functionality of JUNO.</p><p><strong>Methods: </strong>In order to accomplish this, a total of 198 articles were identified. Based on both inclusion and exclusion criteria, 40 articles were finally included in this study.</p><p><strong>Results: </strong>The results showed that during oocyte maturation, the expression levels of JUNO undergo alterations and, in some instances, cross-species gamete fusion is possible. Additionally, it has been observed that exposure of oocytes to factors such as bisphenol A, 17α-ethynylestradiol, diazinon, benzo(a)pyrene, butylparaben, bis(2-ethylhexyl) phthalate, hydroxyurea, dichlorophenol, isoniazid, and para-phenylenediamine disrupt JUNO and decrease the fertilization process rates. Moreover, exposure to ionic radiation, vitrification, and synthetic materials as microplastics has the same effect. Nonetheless, other compounds such as melatonin, mogroside V, cholesterol-loaded methyl-β-cyclodextrin, methyl-β-cyclodextrin, protocatechuic acid, coenzyme Q10, resveratrol, and Shoutai pills have been shown to enhance female fertility in terms of JUNO functionality.</p><p><strong>Conclusion: </strong>In summary, this update highlights the crucial role of JUNO during fertilization and reveals how different factors and experimental procedures affect its activity.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-16"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762972","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}

{"title":"Function of Transforming Growth Factor β2 and β3 in Palatogenesis.","authors":"Miwaki Aoki, Akira Nakajima, Nichika Fukumashi, Risako Okuma, Mitsuru Motoyoshi, Charles F Shuler","doi":"10.1159/000544097","DOIUrl":"https://doi.org/10.1159/000544097","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to examine the transforming growth factor (TGF)-β signaling pathway during secondary palate fusion by transfecting single and double small interfering RNA (siRNAs) for TGF-β2 and -β3. This investigation also focused on understanding the phenotype of palatal development.</p><p><strong>Methods: </strong>siRNAs targeting TGF-β2 and -β3 were used in an organ culture model of fusion of the secondary palate of 13-day embryonic ICR mice cultured for up to 72 h. The palatal shelves were collected at different times following the initiation of organ culture and were examined for TGF-β2 and -β3 gene expression. Downstream signaling was characterized using Western blotting and PCR.</p><p><strong>Results: </strong>In the double siRNA-treated palatal shelves, approximately 90% (91% anterior, 89% posterior with phenotype A) showed fusion failure in hematoxylin and eosin staining. Phosphorylation of Smad-dependent and -independent signaling showed a significant reduction in phosphorylation in double knockdown palate organ cultures when compared to single knockdown cultures. Although, the expression of matrix metalloproteinase 13 and TIMP2 were small influenced by siTGF-β2, the extracellular matrix and transcription factor expressions showed to be significantly reduced in double knockdown palate compared to single knockdown palates.</p><p><strong>Conclusions: </strong>This study demonstrates that double siRNAs targeting TGF-β2 and -β3 results in phenotypes during secondary palatal fusion and that they could be affected phosphorylation of Smad-dependent and -independent signaling synergistically compared to single knockdown of TGF-β2 and -β3. The results of this study demonstrate important functions during secondary palatal fusion and will contribute to our understanding of the etiology of cleft palate.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-15"},"PeriodicalIF":2.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662368","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}

{"title":"Hindlimb Unloading Reversibly Attenuates Osteogenic Potential of Rat Skeletal Stem and Progenitor Cells ex vivo.","authors":"Elena Markina, Elena Andreeva, Ludmila Buravkova","doi":"10.1159/000545284","DOIUrl":"10.1159/000545284","url":null,"abstract":"<p><strong>Introduction: </strong>Prolonged space flights negatively affect the skeleton. Stromal cells of mesenchymal origin play a crucial role in maintaining homeostasis and in regulating the physiological remodeling of various tissues, and this has particular significance for bone.</p><p><strong>Methods: </strong>Hindlimb unloading (HU) of rats as a ground-based model for simulation of microgravity was implemented. The functional activity of skeletal stem and progenitor cells (SSPCs) from rat femoral bones was assessed in vitro after 2 weeks of HU and after 2 weeks of subsequent recovery of load support (HU + reloading [HU + R]). To characterize the growth of the SSPCs, the number of population doublings (PDs) was calculated. Histochemical detection of the activity of alkaline phosphatase (AP) - an early marker of osteo-differentiation - on day 7, and of extracellular matrix (ECM) mineralization - as a sign of late osteo-differentiation - on day 21, were carried out. Quantitative real-time PCR was performed to detect the expression of the genes encoding proteins associated with the functional activity of osteoprogenitor cells (Pparg, Runx2, Alpl, Cxcl12) and bone tissue homeostasis (Mmp9, Spp1, RANKL, OPG, Ibsp, BMP10, Sost).</p><p><strong>Results: </strong>After HU, a twofold decrease in the PD of the SSPCs, a decrease in AP activity and a significant attenuation of ECM mineralization were detected. There was also significant downregulation of the genes encoding proteins related to bone tissue homeostasis: those for bone matrix proteins (RANKL, OPG, Ibsp), and of the master-genes controlling osteo- and adipo-differentiation (Runx2, Alpl, Pparg), as well as of Mmp9, encoding a regulatory molecule of bone matrix remodeling. By contrast, sclerostin (Sost) was upregulated. After HU + R, the PD, as well as AP activity and the level of ECM mineralization were restored.</p><p><strong>Conclusion: </strong>HU leads to inhibition of the osteoplastic function of SSPCs. The presented data are significant for the elucidation of microgravity-induced mechanisms of bone impairment and for the development of countermeasures for astronauts as well as for osteo-deficient patients after prolonged immobilization.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-14"},"PeriodicalIF":2.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656157","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}