Pub Date : 2024-11-28DOI: 10.1016/j.tice.2024.102643
Jinan Liu , Jiran Wang , Rui Huang , Xueting Jia , Xiaofeng Huang
Tooth eruption, a critical stage in tooth development, is related to osteoclastogenesis. Intraperitoneal injection of Shh agonists into neonatal mice promoted tooth eruption at postnatal day (PN) 15, whereas treatment with the Shh inhibitor (LDE225) suppressed this process. When RAW264.7 osteoclast precursor cells were treated with RANKL, NFATc1 translocated from the cytoplasm to the nucleus and induced cell differentiation into TRAP+ osteoclasts; this process was activated by Shh but inhibited by LDE225. Treating RAW264.7 cells with the p38 inhibitor, BIRB796, also inhibited NFATc1 nuclear localization. p-p38 expression in the alveolar bone of PN3 and PN5 mice was decreased by treatment with LDE225, and RAW264.7 cell differentiation was reduced by BIRB796, regardless of treatment with Shh. Furthermore, Shh activated p38 signaling pathway in RAW264.7 cells, while p38 phosphorylation was reduced by LDE225, which ultimately inhibited osteoclast precursor differentiation. Therefore, we concluded that Shh promotes osteoclast precursor differentiation via the p38-NFATc1 signaling pathway.
{"title":"The Shh-p38-NFATc1 signaling pathway is essential for osteoclastogenesis during tooth eruption","authors":"Jinan Liu , Jiran Wang , Rui Huang , Xueting Jia , Xiaofeng Huang","doi":"10.1016/j.tice.2024.102643","DOIUrl":"10.1016/j.tice.2024.102643","url":null,"abstract":"<div><div>Tooth eruption, a critical stage in tooth development, is related to osteoclastogenesis. Intraperitoneal injection of Shh agonists into neonatal mice promoted tooth eruption at postnatal day (PN) 15, whereas treatment with the Shh inhibitor (LDE225) suppressed this process. When RAW264.7 osteoclast precursor cells were treated with RANKL, NFATc1 translocated from the cytoplasm to the nucleus and induced cell differentiation into TRAP<sup>+</sup> osteoclasts; this process was activated by Shh but inhibited by LDE225. Treating RAW264.7 cells with the p38 inhibitor, BIRB796, also inhibited NFATc1 nuclear localization. p-p38 expression in the alveolar bone of PN3 and PN5 mice was decreased by treatment with LDE225, and RAW264.7 cell differentiation was reduced by BIRB796, regardless of treatment with Shh. Furthermore, Shh activated p38 signaling pathway in RAW264.7 cells, while p38 phosphorylation was reduced by LDE225, which ultimately inhibited osteoclast precursor differentiation. Therefore, we concluded that Shh promotes osteoclast precursor differentiation via the p38-NFATc1 signaling pathway.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"92 ","pages":"Article 102643"},"PeriodicalIF":2.7,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142747166","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}
Pub Date : 2024-11-26DOI: 10.1016/j.tice.2024.102638
Ganesh Parasuraman , Mariya Sneha Rani J , Merin Mary Zachariah , Abel Livingston , Elizabeth Vinod
Purpose
In cartilage research, three-dimensional (3D) culture models are pivotal for assessing chondrogenic differentiation potential. Standard pellet cultures, despite their utility, pose challenges like uneven differentiation and handling difficulties. This study explores the use of Matrigel, an extracellular matrix-based hydrogel, to encapsulate fibronectin adhesion assay-derived chondroprogenitors (FAA-CPs) and evaluate their chondrogenic differentiation potential.
Methods
FAA-CPs, isolated from human articular cartilage and expanded to passage 2, were either polymerized in Matrigel or cultured as standard pellets. Both groups underwent chondrogenic differentiation for 28 days and osteogenic differentiation for 21 days. Comprehensive analyses included histological staining, gene expression (SOX-9, ACAN, COL2A1 for chondrogenesis; COL1A1, RUNX2, COL10A1 for osteogenesis), and biochemical assays for glycosaminoglycans (GAG) and Collagen type II.
Results
The results demonstrated that Matrigel-encapsulated FAA-CPs achieved greater GAG accumulation, as evidenced by enhanced Alcian Blue and Safranin O staining, compared to standard pellets. However, the Collagen type II deposition, both histologically and quantitatively, was reduced in Matrigel constructs. Gene expression analysis showed no significant differences in key chondrogenic and osteogenic markers between the two groups. Despite improved handling and GAG deposition, Matrigel did not enhance uniform chondrogenic differentiation nor offer significant benefits for osteogenic differentiation, showing comparable hypertrophic markers to the standard method.
Conclusion
While Matrigel encapsulation offers advantages in handling and enhances GAG accumulation quantitatively, these benefits were not reflected in staining results. Furthermore, Matrigel did not significantly outperform standard pellet cultures in chondrogenic or osteogenic differentiation. These findings suggest a need for further refinement and in vivo validation.
{"title":"Matrigel-encapsulated articular cartilage derived fibronectin adhesion assay derived chondroprogenitors for enhanced chondrogenic differentiation: An in vitro evaluation","authors":"Ganesh Parasuraman , Mariya Sneha Rani J , Merin Mary Zachariah , Abel Livingston , Elizabeth Vinod","doi":"10.1016/j.tice.2024.102638","DOIUrl":"10.1016/j.tice.2024.102638","url":null,"abstract":"<div><h3>Purpose</h3><div>In cartilage research, three-dimensional (3D) culture models are pivotal for assessing chondrogenic differentiation potential. Standard pellet cultures, despite their utility, pose challenges like uneven differentiation and handling difficulties. This study explores the use of Matrigel, an extracellular matrix-based hydrogel, to encapsulate fibronectin adhesion assay-derived chondroprogenitors (FAA-CPs) and evaluate their chondrogenic differentiation potential.</div></div><div><h3>Methods</h3><div>FAA-CPs, isolated from human articular cartilage and expanded to passage 2, were either polymerized in Matrigel or cultured as standard pellets. Both groups underwent chondrogenic differentiation for 28 days and osteogenic differentiation for 21 days. Comprehensive analyses included histological staining, gene expression (SOX-9, ACAN, COL2A1 for chondrogenesis; COL1A1, RUNX2, COL10A1 for osteogenesis), and biochemical assays for glycosaminoglycans (GAG) and Collagen type II.</div></div><div><h3>Results</h3><div>The results demonstrated that Matrigel-encapsulated FAA-CPs achieved greater GAG accumulation, as evidenced by enhanced Alcian Blue and Safranin O staining, compared to standard pellets. However, the Collagen type II deposition, both histologically and quantitatively, was reduced in Matrigel constructs. Gene expression analysis showed no significant differences in key chondrogenic and osteogenic markers between the two groups. Despite improved handling and GAG deposition, Matrigel did not enhance uniform chondrogenic differentiation nor offer significant benefits for osteogenic differentiation, showing comparable hypertrophic markers to the standard method.</div></div><div><h3>Conclusion</h3><div>While Matrigel encapsulation offers advantages in handling and enhances GAG accumulation quantitatively, these benefits were not reflected in staining results. Furthermore, Matrigel did not significantly outperform standard pellet cultures in chondrogenic or osteogenic differentiation. These findings suggest a need for further refinement and in vivo validation.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"92 ","pages":"Article 102638"},"PeriodicalIF":2.7,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142747165","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}
Pub Date : 2024-11-26DOI: 10.1016/j.tice.2024.102642
Huasong Bai , Tong Liu , Hengyan Wang , Yunliang Li , Zhanzhong Wang
Osteoarthritis (OA) is a pervasive degenerative joint disease affecting companion animals, characterized by chronic inflammation and cartilage degradation. However, the effectiveness of chondroitin sulfate (CS) in treating OA in dogs and cats remains controversial. This study aimed to determine the therapeutic effects and molecular mechanisms of CS on lipopolysaccharide (LPS)-induced inflammation in feline and canine articular chondrocytes (FAC and CAC) at the cellular level in vitro. Our findings demonstrated that CS treatment (800 µg/mL) significantly enhanced cell viability and reduced oxidative stress in FAC and CAC, as evidenced by decreased levels of reactive oxygen species and increased activities of antioxidant enzymes. Furthermore, CS treatment effectively suppressed LPS-induced secretion of pro-inflammatory cytokines, including interleukin-1, tumor necrosis factor-α, interleukin-8, interleukin-10, and matrix metalloproteinases-3, and reduced apoptosis, as confirmed by fluorescence staining and flow cytometry. Transcriptomic analysis revealed that CS upregulated neurotrophic signaling pathways, promoting cell survival and proliferation. Metabolomic analysis indicated that CS treatment upregulated metabolites associated with glycerophospholipid and purine metabolism, suggesting enhanced membrane integrity and energy metabolism. Conversely, pathways involved in protein catabolism and arachidonic acid metabolism were downregulated, indicating a reduction in inflammatory mediators. Collectively, these findings elucidate the multifaceted role of CS in modulating chondrocyte metabolism and inflammatory responses, highlighting its potential to alleviate OA.
{"title":"Chondroitin sulfate alleviated lipopolysaccharide-induced arthritis in feline and canine articular chondrocytes through regulation of neurotrophic signaling pathways and apoptosis","authors":"Huasong Bai , Tong Liu , Hengyan Wang , Yunliang Li , Zhanzhong Wang","doi":"10.1016/j.tice.2024.102642","DOIUrl":"10.1016/j.tice.2024.102642","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a pervasive degenerative joint disease affecting companion animals, characterized by chronic inflammation and cartilage degradation. However, the effectiveness of chondroitin sulfate (CS) in treating OA in dogs and cats remains controversial. This study aimed to determine the therapeutic effects and molecular mechanisms of CS on lipopolysaccharide (LPS)-induced inflammation in feline and canine articular chondrocytes (FAC and CAC) at the cellular level <em>in vitro</em>. Our findings demonstrated that CS treatment (800 µg/mL) significantly enhanced cell viability and reduced oxidative stress in FAC and CAC, as evidenced by decreased levels of reactive oxygen species and increased activities of antioxidant enzymes. Furthermore, CS treatment effectively suppressed LPS-induced secretion of pro-inflammatory cytokines, including interleukin-1, tumor necrosis factor-α, interleukin-8, interleukin-10, and matrix metalloproteinases-3, and reduced apoptosis, as confirmed by fluorescence staining and flow cytometry. Transcriptomic analysis revealed that CS upregulated neurotrophic signaling pathways, promoting cell survival and proliferation. Metabolomic analysis indicated that CS treatment upregulated metabolites associated with glycerophospholipid and purine metabolism, suggesting enhanced membrane integrity and energy metabolism. Conversely, pathways involved in protein catabolism and arachidonic acid metabolism were downregulated, indicating a reduction in inflammatory mediators. Collectively, these findings elucidate the multifaceted role of CS in modulating chondrocyte metabolism and inflammatory responses, highlighting its potential to alleviate OA.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"91 ","pages":"Article 102642"},"PeriodicalIF":2.7,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721555","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}
Pub Date : 2024-11-23DOI: 10.1016/j.tice.2024.102637
Yong Chen, Suipeng Li, Xuqing Hou, Yinfeng Jia
Endothelial dysfunction is commonly perceived as a precursor in the process of hypertension, a severe cardiovascular disorder. Phosphodiesterase 4B (PDE4B) inactivation has been proposed to exert cardioprotective effects and prevent pulmonary hypertension. However, the role of PDE4B in endothelial dysfunction in hypertension remains inexplicit, which will be investigated in the present work. In angiotensin II (Ang II)-induced human umbilical vein endothelial cells (HUVECs), RT-qPCR and Western blotting were used to analyze PDE4B expression. CCK-8 method was used to detect cell viability. Flow cytometry assay and Caspase 3 assay kit were used to detect cellular apoptotic level. Wound healing and tube formation assays were respectively used to detect cell migration and angiogenesis. Western blotting and corresponding assay kits were respectively used to analyze the expressions and contents of endothelial dysfunction markers. JC-1 assay, RT-qPCR and relevant assay kit were respectively used to detect mitochondrial membrane potential (ΔΨm), quantify mitochondrial DNA (mtDNA) copy number and mitochondrial permeability transition pore (mPTP) opening. Besides, Western blotting was used to analyze the expressions of endoplasmic reticulum stress (ERS) and AMP-activated protein kinase (AMPK)/sirtuin 1 (Sirt1)/nuclear factor-erythroid 2 related factor 2 (Nrf2)/antioxidant response element (ARE) signaling-associated proteins. PDE4B expression was increased in Ang II- induced HUVECs. PDE4B knockdown promoted the viability, migration, angiogenesis while inhibiting the apoptosis, endothelial dysfunction, ERS and mitochondrial damage in Ang II-induced HUVECs. Additionally, PDE4B silence activated AMPK/Sirt1/Nrf2/ARE pathway and AMPK inhibitor Compound C (CC) partially reversed the effects of PDE4B down-regulation on Ang II-induced HUVECs. Conclusively, PDE4B inhibition might protect against Ang II-induced endothelial dysfunction in HUVECs via up-regulating AMPK/Sirt1/Nrf2/ARE pathway, which might be mediated by the suppression of ERS and mitochondrial damage.
内皮功能障碍通常被认为是高血压这一严重心血管疾病的前兆。磷酸二酯酶 4B (PDE4B) 失活被认为具有保护心脏和预防肺动脉高压的作用。然而，PDE4B 在高血压内皮功能障碍中的作用尚不明确，本研究将对此进行研究。在血管紧张素 II（Ang II）诱导的人脐静脉内皮细胞（HUVECs）中，采用 RT-qPCR 和 Western 印迹法分析 PDE4B 的表达。采用 CCK-8 法检测细胞活力。流式细胞术检测和 Caspase 3 检测试剂盒用于检测细胞凋亡水平。伤口愈合和管形成试验分别用于检测细胞迁移和血管生成。Western 印迹法和相应的检测试剂盒分别用于分析内皮功能障碍标志物的表达和含量。JC-1检测、RT-qPCR和相关检测试剂盒分别用于检测线粒体膜电位（ΔΨm）、线粒体DNA（mtDNA）拷贝数定量和线粒体通透性转换孔（mPTP）开放。此外，还采用 Western 印迹法分析了内质网应激（ERS）和 AMPK 激活蛋白激酶（AMPK）/sirtuin 1（Sirt1）/核因子红细胞 2 相关因子 2（Nrf2）/抗氧化反应元件（ARE）信号相关蛋白的表达。在 Ang II 诱导的 HUVECs 中，PDE4B 的表达增加。PDE4B 敲除可促进 Ang II 诱导的 HUVECs 的活力、迁移和血管生成，同时抑制其凋亡、内皮功能障碍、ERS 和线粒体损伤。此外，PDE4B 沉默激活了 AMPK/Sirt1/Nrf2/ARE 通路，AMPK 抑制剂化合物 C（CC）部分逆转了 PDE4B 下调对 Ang II 诱导的 HUVECs 的影响。结论是，PDE4B抑制可通过上调AMPK/Sirt1/Nrf2/ARE通路保护HUVECs免受Ang II诱导的内皮功能障碍，而AMPK/Sirt1/Nrf2/ARE通路可能是通过抑制ERS和线粒体损伤介导的。
{"title":"PDE4B abrogation extenuates angiotensin II-induced endothelial dysfunction related to hypertension through up-regulation of AMPK/Sirt1/Nrf2/ARE signaling","authors":"Yong Chen, Suipeng Li, Xuqing Hou, Yinfeng Jia","doi":"10.1016/j.tice.2024.102637","DOIUrl":"10.1016/j.tice.2024.102637","url":null,"abstract":"<div><div>Endothelial dysfunction is commonly perceived as a precursor in the process of hypertension, a severe cardiovascular disorder. Phosphodiesterase 4B (PDE4B) inactivation has been proposed to exert cardioprotective effects and prevent pulmonary hypertension. However, the role of PDE4B in endothelial dysfunction in hypertension remains inexplicit, which will be investigated in the present work. In angiotensin II (Ang II)-induced human umbilical vein endothelial cells (HUVECs), RT-qPCR and Western blotting were used to analyze PDE4B expression. CCK-8 method was used to detect cell viability. Flow cytometry assay and Caspase 3 assay kit were used to detect cellular apoptotic level. Wound healing and tube formation assays were respectively used to detect cell migration and angiogenesis. Western blotting and corresponding assay kits were respectively used to analyze the expressions and contents of endothelial dysfunction markers. JC-1 assay, RT-qPCR and relevant assay kit were respectively used to detect mitochondrial membrane potential (ΔΨm), quantify mitochondrial DNA (mtDNA) copy number and mitochondrial permeability transition pore (mPTP) opening. Besides, Western blotting was used to analyze the expressions of endoplasmic reticulum stress (ERS) and AMP-activated protein kinase (AMPK)/sirtuin 1 (Sirt1)/nuclear factor-erythroid 2 related factor 2 (Nrf2)/antioxidant response element (ARE) signaling-associated proteins. PDE4B expression was increased in Ang II- induced HUVECs. PDE4B knockdown promoted the viability, migration, angiogenesis while inhibiting the apoptosis, endothelial dysfunction, ERS and mitochondrial damage in Ang II-induced HUVECs. Additionally, PDE4B silence activated AMPK/Sirt1/Nrf2/ARE pathway and AMPK inhibitor Compound C (CC) partially reversed the effects of PDE4B down-regulation on Ang II-induced HUVECs. Conclusively, PDE4B inhibition might protect against Ang II-induced endothelial dysfunction in HUVECs via up-regulating AMPK/Sirt1/Nrf2/ARE pathway, which might be mediated by the suppression of ERS and mitochondrial damage.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"91 ","pages":"Article 102637"},"PeriodicalIF":2.7,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721553","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}
Pub Date : 2024-11-22DOI: 10.1016/j.tice.2024.102635
Hesham M. Hassan , Mahmoud El Safadi , Warda Mustfa , Shahaba Tehreem , Giorgio Antoniolli , Arifa Mehreen , Adnan Ali , Ahmed Al-Emam
Metribuzin (MBN) is a selective herbicide that adversely damages the vital organs of the body including the liver. Pratensein (PTN) is a novel flavonoid that exhibits marvelous medicinal properties. This experimental trial commenced to elucidate the pharmacotherapeutic strength of PTN to counteract MBN provoked liver toxicity in rats. Thirty-six male albino rats (Rattus norvegicus) were categorized into four groups i.e., the control, MBN (133.33 mg/kg), MBN (133.33 mg/kg) + PTN (20 mg/kg) and PTN (20 mg/kg) alone treated group. Our findings revealed that MBN exposure promoted the expressions of Keap-1 as well as concentrations of ROS and MDA while reducing the gene expressions of Nrf-2 as well as activities of catalase (CAT), glutathione Peroxidase (GPx), glutathione reductase (GSR), heme oxygenase-1 (HO-1), superoxide dismutase (SOD) and glutathione (GSH) contents. The levels of albumin and total proteins were reduced whereas the levels of alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were enhanced following the MBN administration. Moreover, the gene expression of transforming growth Factor–β1 (TGF-β1), matrix metallopeptidase-2 (MMP-2), matrix metallopeptidase-9 (MMP-9), collagen, type I, alpha 1 and type-3 alpha were escalated in response to MBN intoxication. Furthermore, MBN administration cause a sudden upregulation in the levels of NF-κB, IL-1β, TNF-α, IL-6 & COX-2. Besides, MBN exposure enhanced the gene expression of Bax and Caspase-3 while reducing the gene expression of PI3K, Akt and Bcl-2. Additionally, MBN exposure dysregulated the normal histology of liver. However, PTN treatment notably protected the hepatic tissues via regulating abovementioned dysregulations due to its marvelous ROS scavenging potential.
{"title":"Pharmacotherapeutic potential of pratensein to avert metribuzin instigated hepatotoxicity via regulating TGF-β1, PI3K/Akt, Nrf-2/Keap-1 and NF-κB pathway","authors":"Hesham M. Hassan , Mahmoud El Safadi , Warda Mustfa , Shahaba Tehreem , Giorgio Antoniolli , Arifa Mehreen , Adnan Ali , Ahmed Al-Emam","doi":"10.1016/j.tice.2024.102635","DOIUrl":"10.1016/j.tice.2024.102635","url":null,"abstract":"<div><div>Metribuzin (MBN) is a selective herbicide that adversely damages the vital organs of the body including the liver. Pratensein (PTN) is a novel flavonoid that exhibits marvelous medicinal properties. This experimental trial commenced to elucidate the pharmacotherapeutic strength of PTN to counteract MBN provoked liver toxicity in rats. Thirty-six male albino rats (<em>Rattus norvegicus</em>) were categorized into four groups i.e., the control, MBN (133.33 mg/kg), MBN (133.33 mg/kg) + PTN (20 mg/kg) and PTN (20 mg/kg) alone treated group. Our findings revealed that MBN exposure promoted the expressions of Keap-1 as well as concentrations of ROS and MDA while reducing the gene expressions of Nrf-2 as well as activities of catalase (CAT), glutathione Peroxidase (GPx), glutathione reductase (GSR), heme oxygenase-1 (HO-1), superoxide dismutase (SOD) and glutathione (GSH) contents. The levels of albumin and total proteins were reduced whereas the levels of alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were enhanced following the MBN administration. Moreover, the gene expression of transforming growth Factor–β1 (TGF-β1), matrix metallopeptidase-2 (MMP-2), matrix metallopeptidase-9 (MMP-9), collagen, type I, alpha 1 and type-3 alpha were escalated in response to MBN intoxication. Furthermore, MBN administration cause a sudden upregulation in the levels of NF-κB, IL-1β, TNF-α, IL-6 & COX-2. Besides, MBN exposure enhanced the gene expression of Bax and Caspase-3 while reducing the gene expression of PI3K, Akt and Bcl-2. Additionally, MBN exposure dysregulated the normal histology of liver. However, PTN treatment notably protected the hepatic tissues via regulating abovementioned dysregulations due to its marvelous ROS scavenging potential.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"91 ","pages":"Article 102635"},"PeriodicalIF":2.7,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721556","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}
Pub Date : 2024-11-22DOI: 10.1016/j.tice.2024.102636
Rui Zhang , Jie Chen , Yuanyuan Chen , Yangyang Li
The therapeutic effectiveness of dental pulp stem cells (DPSCs) is limited. Sirtuin 7 (SIRT7) has been reported to be associated with a variety of age-related diseases. We aimed to identify the regulatory role of SIRT7 in DPSC senescence and investigate the underlying mechanism. DPSCs were isolated from healthy adults, the stem markers were verified by flow cytomerty analysis. Replicative senescence was induced in DPSCs by serial passage and cells were analyzed at PD16 and 54. DPSC senescence was evaluated by observing senescence-associated β-galactosidase (SA-β-gal) and telomerase reverse transcriptase (TERT) activity. Meanwhile, the markers of senescence levels were monitored by western blotting assay. SIRT7 protein was pulled-down, and the binding relationship between SIRT7 and ROCK1 was verified by immunoprecipitation and western blotting methods. Replicative senescence was induced in DPSCs at PD54. The number of SA-β-gal stained DPSCs significantly increased in the PD54 group while the level of TERT activity was decreased. The cyclin-dependent kinase inhibitors p53, p21, and p16, which are markers of senescence, were markedly up-regulated at PD54. SIRT7 was also found to be lowly expressed at PD54. Inhibition of SIRT7 significantly accelerated the senescence of DPSCs. Moreover, SIRT7 can bind with ROCK1, and SIRT7 could lead to ROCK1 desuccinylation at K520. Inhibited ROCK1 significantly reversed the effects of SIRT7 knockdown on regulating DPSCs senescence. Our results demonstrate that the SIRT7/ROCK1 axis plays a key role in the regulation of DPSC senescence and provide a candidate target to improve the functional and therapeutic potential of DPSCs.
{"title":"SIRT7 promotes dental pulp stem cells replicative senescence through desuccinylation of ROCK1","authors":"Rui Zhang , Jie Chen , Yuanyuan Chen , Yangyang Li","doi":"10.1016/j.tice.2024.102636","DOIUrl":"10.1016/j.tice.2024.102636","url":null,"abstract":"<div><div>The therapeutic effectiveness of dental pulp stem cells (DPSCs) is limited. Sirtuin 7 (SIRT7) has been reported to be associated with a variety of age-related diseases. We aimed to identify the regulatory role of SIRT7 in DPSC senescence and investigate the underlying mechanism. DPSCs were isolated from healthy adults, the stem markers were verified by flow cytomerty analysis. Replicative senescence was induced in DPSCs by serial passage and cells were analyzed at PD16 and 54. DPSC senescence was evaluated by observing senescence-associated β-galactosidase (SA-β-gal) and telomerase reverse transcriptase (TERT) activity. Meanwhile, the markers of senescence levels were monitored by western blotting assay. SIRT7 protein was pulled-down, and the binding relationship between SIRT7 and ROCK1 was verified by immunoprecipitation and western blotting methods. Replicative senescence was induced in DPSCs at PD54. The number of SA-β-gal stained DPSCs significantly increased in the PD54 group while the level of TERT activity was decreased. The cyclin-dependent kinase inhibitors p53, p21, and p16, which are markers of senescence, were markedly up-regulated at PD54. SIRT7 was also found to be lowly expressed at PD54. Inhibition of SIRT7 significantly accelerated the senescence of DPSCs. Moreover, SIRT7 can bind with ROCK1, and SIRT7 could lead to ROCK1 desuccinylation at K520. Inhibited ROCK1 significantly reversed the effects of SIRT7 knockdown on regulating DPSCs senescence. Our results demonstrate that the SIRT7/ROCK1 axis plays a key role in the regulation of DPSC senescence and provide a candidate target to improve the functional and therapeutic potential of DPSCs.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"92 ","pages":"Article 102636"},"PeriodicalIF":2.7,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142747170","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}
Non-weightbearing or immobilization after anterior cruciate ligament (ACL) reconstruction accelerates cartilage degeneration. However, it is unclear whether these adverse effects are reversed by reloading or remobilization. Moreover, it is unknown whether the combination of non-weightbearing and immobilization after ACL reconstruction has synergistic effects on cartilage degeneration. We aimed to determine 1) the long-term effects of reloading or remobilization following short-term non-weightbearing or immobilization after ACL reconstruction on cartilage degeneration and 2) the combined effects of non-weightbearing and immobilization on cartilage degeneration. We divided ACL-reconstructed rats into four groups: no intervention, non-weightbearing, joint immobilization, and non-weightbearing plus immobilization. Non-weightbearing and immobilization were performed for 2 weeks, after which all rats were reared without intervention. Untreated rats were used as controls. At 2, 4, or 12 weeks after starting the experiment, cartilage degeneration in the anterior, middle, and posterior regions of the medial tibial plateau was histologically assessed. Two weeks of non-weightbearing or immobilization after ACL reconstruction facilitated cartilage degeneration in the middle and posterior regions compared to those with no intervention. Cartilage degeneration was not reversed by 10 weeks of reloading or remobilization. Compared with non-weightbearing alone, combination of non-weightbearing and immobilization improved cartilage degeneration in the middle region, but worsened it in the posterior region. Cartilage degeneration induced by 2 weeks of non-weightbearing or immobilization after ACL reconstruction was not reversed by reloading or remobilization. Thus, to reduce cartilage degeneration, non-weightbearing and immobilization should be avoided after ACL reconstruction, even for short-term.
{"title":"The effects of short-term non-weightbearing and immobilization after anterior cruciate ligament reconstruction on articular cartilage: Long-term observation after reloading and remobilization","authors":"Akinori Kaneguchi, Ryo Okahara, Nanami Masuhara, Yoshika Doi, Kaoru Yamaoka, Junya Ozawa","doi":"10.1016/j.tice.2024.102628","DOIUrl":"10.1016/j.tice.2024.102628","url":null,"abstract":"<div><div>Non-weightbearing or immobilization after anterior cruciate ligament (ACL) reconstruction accelerates cartilage degeneration. However, it is unclear whether these adverse effects are reversed by reloading or remobilization. Moreover, it is unknown whether the combination of non-weightbearing and immobilization after ACL reconstruction has synergistic effects on cartilage degeneration. We aimed to determine 1) the long-term effects of reloading or remobilization following short-term non-weightbearing or immobilization after ACL reconstruction on cartilage degeneration and 2) the combined effects of non-weightbearing and immobilization on cartilage degeneration. We divided ACL-reconstructed rats into four groups: no intervention, non-weightbearing, joint immobilization, and non-weightbearing plus immobilization. Non-weightbearing and immobilization were performed for 2 weeks, after which all rats were reared without intervention. Untreated rats were used as controls. At 2, 4, or 12 weeks after starting the experiment, cartilage degeneration in the anterior, middle, and posterior regions of the medial tibial plateau was histologically assessed. Two weeks of non-weightbearing or immobilization after ACL reconstruction facilitated cartilage degeneration in the middle and posterior regions compared to those with no intervention. Cartilage degeneration was not reversed by 10 weeks of reloading or remobilization. Compared with non-weightbearing alone, combination of non-weightbearing and immobilization improved cartilage degeneration in the middle region, but worsened it in the posterior region. Cartilage degeneration induced by 2 weeks of non-weightbearing or immobilization after ACL reconstruction was not reversed by reloading or remobilization. Thus, to reduce cartilage degeneration, non-weightbearing and immobilization should be avoided after ACL reconstruction, even for short-term.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"92 ","pages":"Article 102628"},"PeriodicalIF":2.7,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142747160","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}
Glial cells missing 2 (GCM2) has been identified as an essential factor for parathyroid differentiation, and GCM2 silencing in parathyroid cells decreases calcium-sensing receptor (CaSR) expression. However, the role of GCM2 in parathyroid differentiation from induced pluripotent stem cells (iPSCs) is unclear. Here, we investigated the role of GCM2 in parathyroid differentiation from iPSCs using the Tet-On 3 G system. We confirmed that iPS cells transfected with GCM2/TRE3G and pCMV-Tet3G vectors express GCM2 in a doxycycline-dependent manner. Though parathyroid glands derive from the endoderm and differentiate via the third pharyngeal arch (PPE), overexpression of GCM2 in iPSCs significantly abolished the suppression of OCT4 and SOX2, suggesting inhibition of endodermal differentiation. GCM2 overexpression at the stage of differentiation into the third PPE also increased the expression levels of CaSR and parathyroid hormone, and increased the number of CaSR+/EpCAM+ cells. These results suggest that GCM2 regulates parathyroid differentiation after endoderm differentiation rather than at an earlier stage.
{"title":"The role of glial cells missing 2 in induced pluripotent stem cell parathyroid differentiation","authors":"Tadashi Kato , Ryusuke Nakatsuka , Rong Zhang , Yasushi Uemura , Hiromi Yamashita , Yoshikazu Matsuoka , Yasumasa Shirouzu , Tatsuya Fujioka , Fumiyuki Hattori , Hiroaki Ogata , Akiko Sakashita , Hirokazu Honda , Hirofumi Hitomi","doi":"10.1016/j.tice.2024.102634","DOIUrl":"10.1016/j.tice.2024.102634","url":null,"abstract":"<div><div>Glial cells missing 2 (GCM2) has been identified as an essential factor for parathyroid differentiation, and GCM2 silencing in parathyroid cells decreases calcium-sensing receptor (CaSR) expression. However, the role of GCM2 in parathyroid differentiation from induced pluripotent stem cells (iPSCs) is unclear. Here, we investigated the role of GCM2 in parathyroid differentiation from iPSCs using the Tet-On 3 G system. We confirmed that iPS cells transfected with GCM2/TRE3G and pCMV-Tet3G vectors express GCM2 in a doxycycline-dependent manner. Though parathyroid glands derive from the endoderm and differentiate via the third pharyngeal arch (PPE), overexpression of GCM2 in iPSCs significantly abolished the suppression of <em>OCT4</em> and <em>SOX2</em>, suggesting inhibition of endodermal differentiation. GCM2 overexpression at the stage of differentiation into the third PPE also increased the expression levels of CaSR and parathyroid hormone, and increased the number of CaSR<sup>+</sup>/EpCAM<sup>+</sup> cells. These results suggest that GCM2 regulates parathyroid differentiation after endoderm differentiation rather than at an earlier stage.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"92 ","pages":"Article 102634"},"PeriodicalIF":2.7,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142747167","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}
Pub Date : 2024-11-21DOI: 10.1016/j.tice.2024.102633
Tao Zhang, Long Zhao, Xiaoping Tang
We elucidate the role of the BNC1 gene in glioma and its potential mechanism. The expression levels of BNC1 in patients with glioma or corresponding cell lines were down-regulated. High BNC1 expression increased survival rate in patients with glioma. BNC1 gene reduced cell proliferation, and enhanced ferroptosis of glioma cells through the induction of TCF21/PI3K signaling pathway. Meanwhile, BNC1 gene could decline tumor proliferation in mice model of glioma. The ferroptosis inhibitor alleviated the impact of BNC1 on glioma ferroptosis, while the ferroptosis agonist weakened the effect of BNC1 on glioma ferroptosis. SiTCF21 also declined the effects of BNC1 on ferroptosis of glioma. The enhanced expression of TCF21 also inhibited the effect of BNC1 on ferroptosis of glioma. BNC1 protein interlinked with TCF21 protein, and bioluminescence imaging demonstrated that BNC1 enhanced TCF21 expression in the brain tissue of the mouse model of glioma. In conclusion, BNC1 reduced cell proliferation, and increased ferroptosis of glioma cells by TCF21/PI3K signaling pathway, may be a feasible strategy to treat glioma.
{"title":"Down-regulated BNC1 promotes glioma by inhibiting ferroptosis via TCF21/PI3K signaling pathway BNC1TCF21PI3K","authors":"Tao Zhang, Long Zhao, Xiaoping Tang","doi":"10.1016/j.tice.2024.102633","DOIUrl":"10.1016/j.tice.2024.102633","url":null,"abstract":"<div><div>We elucidate the role of the <em>BNC1</em> gene in glioma and its potential mechanism. The expression levels of <em>BNC1</em> in patients with glioma or corresponding cell lines were down-regulated. High <em>BNC1</em> expression increased survival rate in patients with glioma. <em>BNC1</em> gene reduced cell proliferation, and enhanced ferroptosis of glioma cells through the induction of <em>TCF21</em>/<em>PI3K</em> signaling pathway. Meanwhile, <em>BNC1</em> gene could decline tumor proliferation in mice model of glioma. The ferroptosis inhibitor alleviated the impact of <em>BNC1</em> on glioma ferroptosis, while the ferroptosis agonist weakened the effect of <em>BNC1</em> on glioma ferroptosis. Si<em>TCF21</em> also declined the effects of <em>BNC1</em> on ferroptosis of glioma. The enhanced expression of <em>TCF21</em> also inhibited the effect of <em>BNC1</em> on ferroptosis of glioma. <em>BNC1</em> protein interlinked with <em>TCF21</em> protein, and bioluminescence imaging demonstrated that <em>BNC1</em> enhanced <em>TCF21</em> expression in the brain tissue of the mouse model of glioma. In conclusion, <em>BNC1</em> reduced cell proliferation, and increased ferroptosis of glioma cells by <em>TCF21</em>/<em>PI3K</em> signaling pathway, may be a feasible strategy to treat glioma.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"91 ","pages":"Article 102633"},"PeriodicalIF":2.7,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721554","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}
Pub Date : 2024-11-21DOI: 10.1016/j.tice.2024.102630
Indyaswan Tegar Suryaningtyas , Jae-Young Je
Non-alcoholic fatty liver disease (NAFLD) is a progressive condition, advancing from simple hepatic lipid accumulation to inflammation, fibrosis, and increased risk of mortality. This study explores the therapeutic efficacy of bioactive peptides PIISVYWK (P1) and FSVVPSPK (P2) in ameliorating NAFLD in both oleic acid-treated HepG2 cells and high-fat diet (HFD)-induced mice. Our findings demonstrated that P1 and P2 significantly reduced hepatic fat deposition, enhanced lipolysis by promoting the release of free glycerol and free fatty acids, and suppressed key de novo lipogenesis-related proteins, including peroxisome proliferator-activated receptor γ (PPARγ), CCAAT-enhancer-binding protein α (C/EBPα), sterol regulatory element-binding protein 1 (SREBP-1), and fatty acid synthase (FAS). Furthermore, both peptides stimulated fatty acid oxidation via phosphorylation of AMP-activated protein kinase (AMPK) and hormone-sensitive lipase (HSL). Notably, reductions in body and liver weight, along with improved cholesterol profiles and liver function markers (alanine transaminase and aspartate aminotransferase), were observed in HFD mice. Additionally, P1 and P2 significantly attenuated the production of pro-inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in both in vitro and in vivo models. Collectively, these results highlight the potent therapeutic potential of P1 and P2 in mitigating NAFLD progression, offering a promising intervention for this increasingly prevalent metabolic disorder.
{"title":"Therapeutic effects of blue mussel-derived peptides (PIISVYWK and FSVVPSPK) on non-alcoholic fatty liver disease by modulating lipid metabolism and inflammation in high-fat diet-induced mice","authors":"Indyaswan Tegar Suryaningtyas , Jae-Young Je","doi":"10.1016/j.tice.2024.102630","DOIUrl":"10.1016/j.tice.2024.102630","url":null,"abstract":"<div><div>Non-alcoholic fatty liver disease (NAFLD) is a progressive condition, advancing from simple hepatic lipid accumulation to inflammation, fibrosis, and increased risk of mortality. This study explores the therapeutic efficacy of bioactive peptides PIISVYWK (P1) and FSVVPSPK (P2) in ameliorating NAFLD in both oleic acid-treated HepG2 cells and high-fat diet (HFD)-induced mice. Our findings demonstrated that P1 and P2 significantly reduced hepatic fat deposition, enhanced lipolysis by promoting the release of free glycerol and free fatty acids, and suppressed key <em>de novo</em> lipogenesis-related proteins, including peroxisome proliferator-activated receptor γ (PPARγ), CCAAT-enhancer-binding protein α (C/EBPα), sterol regulatory element-binding protein 1 (SREBP-1), and fatty acid synthase (FAS). Furthermore, both peptides stimulated fatty acid oxidation via phosphorylation of AMP-activated protein kinase (AMPK) and hormone-sensitive lipase (HSL). Notably, reductions in body and liver weight, along with improved cholesterol profiles and liver function markers (alanine transaminase and aspartate aminotransferase), were observed in HFD mice. Additionally, P1 and P2 significantly attenuated the production of pro-inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in both <em>in vitro</em> and <em>in vivo</em> models. Collectively, these results highlight the potent therapeutic potential of P1 and P2 in mitigating NAFLD progression, offering a promising intervention for this increasingly prevalent metabolic disorder.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"91 ","pages":"Article 102630"},"PeriodicalIF":2.7,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695839","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}
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