Differentiation最新文献_第2页

RANKL promotes MT2 degradation and ROS production in osteoclast precursors through Beclin1-dependent autophagy RANKL通过beclin1依赖性自噬促进破骨细胞前体MT2降解和ROS产生

IF 2.2 3区生物学

Differentiation Pub Date : 2025-04-19 DOI: 10.1016/j.diff.2025.100863

Dianshan Ke , Tingwei Gao , Hanhao Dai , Jie Xu, Tie Ke

{"title":"RANKL promotes MT2 degradation and ROS production in osteoclast precursors through Beclin1-dependent autophagy","authors":"Dianshan Ke , Tingwei Gao , Hanhao Dai , Jie Xu, Tie Ke","doi":"10.1016/j.diff.2025.100863","DOIUrl":"10.1016/j.diff.2025.100863","url":null,"abstract":"<div><div>ROS produced under oxidative stress are crucial for osteoclast differentiation. Metallothionein (MT) is a ROS-scavenging molecule. As a member of MT family, MT2 can clear ROS in osteoclast precursors (OCPs) and contributes to osteoclast differentiation. RANKL can promote OCP autophagy. Given the molecular-degrading effect of autophagy, the relationship between RANKL-dependent autophagy, MT2 and ROS during osteoclast differentiation is worth exploring. We depended <em>in vitro</em> RANKL administration and RANKL-overexpressing (Tg-RANKL) mice to observe the effects of RANKL on ROS production, MT2 protein expression, Beclin1 expression and autophagic activity in OCPs. Spautin1 was used to investigate the relationship between Beclin1-dependent autophagy and RANKL-regulated MT2 expression. Osteoclast-targeting MT2-cDNA-AAVs were applied to assess the therapeutic effect of MT2 on Tg-RANKL-related bone loss. The results showed that RANKL promoted ROS production but reduced MT2 protein expression in OCPs. RANKL also enhanced Beclin1 expression and LC3-puncta abundance. Decreased Beclin1 expression with spautin1 blocked RANKL-increased ROS production and osteoclast differentiation and recovered RANKL-decreased MT2 expression. MT2 selective overexpression with CD11b-promoter-MT2-cDNA-AAVs attenuated ROS production and osteoclastogenesis in Tg-RANKL mice and improved bone loss. Overall, RANKL can reduce MT2 protein expression through Beclin1-dependent autophagy, thereby promoting ROS production and osteoclast differentiation; this suggests that MT2-overexpressing small molecule drugs have the potential to treat RANKL-related bone loss.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"143 ","pages":"Article 100863"},"PeriodicalIF":2.2,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The mechanism of EGF in promoting skeletal muscle post-injury regeneration 表皮生长因子促进骨骼肌损伤后再生的机制

IF 2.2 3区生物学

Differentiation Pub Date : 2025-04-07 DOI: 10.1016/j.diff.2025.100862

Huaixin Teng , Yongze Liu , Ruotong Hao , Lu Zhang , Xiaoyu Zhang , Shufeng Li , Shuang Li , Huili Tong

引用次数: 0

Chondrocalcin: Insights into its regulation and multi-function in cartilage and bone 软骨钙素：其在软骨和骨中的调节和多功能的见解

IF 2.2 3区生物学

Differentiation Pub Date : 2025-03-24 DOI: 10.1016/j.diff.2025.100861

Wensha Zhu , Zilong Zhao , Weigang Yuwen , Linlin Qu , Zhiguang Duan , Chenhui Zhu , Daidi Fan

引用次数: 0

Fibroblast growth factor 22 成纤维细胞生长因子22

IF 2.2 3区生物学

Differentiation Pub Date : 2025-03-20 DOI: 10.1016/j.diff.2025.100860

Rise Furuta, Ayumi Miyake

{"title":"Fibroblast growth factor 22","authors":"Rise Furuta, Ayumi Miyake","doi":"10.1016/j.diff.2025.100860","DOIUrl":"10.1016/j.diff.2025.100860","url":null,"abstract":"<div><div>Fibroblast growth factor 22 (FGF22) is a member of the FGF7 subfamily that functions as a paracrine factor and was identified in the human placenta in 2001. The <em>FGF22</em> gene is located on human chromosome 19p13.3, mouse chromosome 10, and zebrafish chromosome 22 and is closely linked to the <em>BSG, HCN2</em>, and <em>POLRMT</em> genes. The gene is composed of three exons, which are common in humans, mice, and zebrafish. However, in humans and mice, FGF22 is produced as two isoforms by alternative splicing, whereas no isoforms have been reported in zebrafish. In humans, <em>FGF22</em> is expressed in the skin, brain, and ovaries, whereas in mice, it is expressed in the skin, brain, retina, spinal cord, and cochlea. Various abnormalities have been reported in these regions in <em>Fgf22</em> mutant mice. In zebrafish, <em>fgf22</em> is expressed in the forebrain, midbrain, and otic vesicles during embryogenesis, and an analysis of knockdown zebrafish models revealed an important role for <em>fgf22</em> in the process of brain formation. As expected from the results of these functional analyses, FGF22 is also associated with human diseases such as depression, spinal cord injury, hearing loss, and cancer.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"143 ","pages":"Article 100860"},"PeriodicalIF":2.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Immune Cell-NSPC interactions: Friend or foe in CNS injury and repair? 免疫细胞- nspc相互作用：中枢神经系统损伤和修复的朋友还是敌人？

IF 2.2 3区生物学

Differentiation Pub Date : 2025-03-14 DOI: 10.1016/j.diff.2025.100855

Chih-Wei Zeng

{"title":"Immune Cell-NSPC interactions: Friend or foe in CNS injury and repair?","authors":"Chih-Wei Zeng","doi":"10.1016/j.diff.2025.100855","DOIUrl":"10.1016/j.diff.2025.100855","url":null,"abstract":"<div><div>Neural stem/progenitor cells (NSPCs) play a crucial role in central nervous system (CNS) development, regeneration, and repair. However, their functionality and therapeutic potential are intricately modulated by interactions with immune cells, particularly macrophages and microglia. Microglia, as CNS-resident macrophages, are distinct from peripheral macrophages in their roles and characteristics, contributing to specialized functions within the CNS. Recent evidence suggests that microglia, as CNS-resident macrophages, contribute to the quality assurance of NSPCs by eliminating stressed or dysfunctional cells, yet the mechanisms underlying this process remain largely unexplored. Furthermore, macrophage polarization states, such as M1 and M2, appear to differentially influence NSPC quality, potentially impacting neurogenesis and regenerative outcomes. Identifying surface markers indicative of NSPC stress could provide a strategy for selecting optimal cells for transplantation therapies. Additionally, <em>in vivo</em> clonal labeling approaches may enable precise tracking of NSPC fate and their interactions with immune cells. Beyond macrophages and microglia, the roles of other immune cells, including T cells and neutrophils, particularly in injury and neurodegenerative disease contexts, in the context of CNS injury and disease are emerging areas of interest. Here, I discuss the emerging evidence supporting the interplay between the immune system and NSPCs, highlighting critical gaps in knowledge and proposing future research directions to harness immune-mediated mechanisms for optimizing neural regeneration and transplantation strategies.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"143 ","pages":"Article 100855"},"PeriodicalIF":2.2,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

FGFR3 signaling is essential for gastric cancer cell triggering the transition of BM-MSCs into tumor-associated MSCs FGFR3信号对于胃癌细胞触发BM-MSCs向肿瘤相关MSCs的转变至关重要

IF 2.2 3区生物学

Differentiation Pub Date : 2025-03-14 DOI: 10.1016/j.diff.2025.100859

Xiang Wang , Xiaoli Cao , Baocheng Zhou , Jingyu Mei , Yuanyuan Li , Xinlan Zhao , Wei Zhu , Feng Huang , Li Sun , Mei Wang

{"title":"FGFR3 signaling is essential for gastric cancer cell triggering the transition of BM-MSCs into tumor-associated MSCs","authors":"Xiang Wang , Xiaoli Cao , Baocheng Zhou , Jingyu Mei , Yuanyuan Li , Xinlan Zhao , Wei Zhu , Feng Huang , Li Sun , Mei Wang","doi":"10.1016/j.diff.2025.100859","DOIUrl":"10.1016/j.diff.2025.100859","url":null,"abstract":"<div><div>Bone marrow-derived mesenchymal stem cells (BM-MSCs) tend to migrate towards tumor sites and interact with tumor cells, thus incorporating into tumor microenvironment by transition into various stromal cells, particularly tumor-associated MSCs. However, the mechanisms involved in this process is still not clarified. Herein, we focused on miR-99a-5p and confirmed its reduction in gastric cancer-associated MSCs (GC-MSCs) compared to BM-MSCs. Under-expression of miR-99a-5p stimulated BM-MSCs transition into GC-MSCs-like cells, while overexpression of this miRNA abrogated tumor-promoting roles of GC-MSCs. miR-99a-5p not only targeted modulation of fibroblast growth factor receptor (FGFR3) but also negatively affected its phosphorylated levels. Suppression of FGFR3 signaling by AZD4547 or siRNA against FGFR3 notably blocked the miR-99a-5p inhibitor-induced BM-MSCs transition and the oncogenic roles of GC-MSCs. However, miR-99a-5p overexpression did not diminish the ability of gastric cancer cells to educate BM-MSCs. The levels of phosphorylated FGFR3, but not total FGFR3, was increased in BM-MSCs educated by gastric cancer cells. AZD4547 significantly suppressed the education capacity of gastric cancer cells on BM-MSCs. Taken together, although manipulating miR-99a-5p to mimic its levels in GC-MSCs promotes the transition of BM-MSCs into GC-MSCs-like cells, FGFR3 signaling, rather than miR-99a-5p, is unexpectedly essential for the education of BM-MSCs by gastric cancer cells. This discovery provides a novel mechanism underlying the transition of BM-MSCs into tumor-associated MSCs and identifies potential therapeutic targets for gastric cancer.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"143 ","pages":"Article 100859"},"PeriodicalIF":2.2,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NSAID-mediated cyclooxygenase inhibition disrupts ectodermal derivative formation in axolotl embryos 非甾体抗炎药介导的环加氧酶抑制破坏美西螈胚胎外胚层衍生物的形成

IF 2.2 3区生物学

Differentiation Pub Date : 2025-03-14 DOI: 10.1016/j.diff.2025.100856

Emma J. Marshall , Raneesh Ramarapu , Tess A. Leathers , Nikolas Morrison-Welch , Kathryn Sandberg , Maxim Kawashima , Crystal D. Rogers

{"title":"NSAID-mediated cyclooxygenase inhibition disrupts ectodermal derivative formation in axolotl embryos","authors":"Emma J. Marshall , Raneesh Ramarapu , Tess A. Leathers , Nikolas Morrison-Welch , Kathryn Sandberg , Maxim Kawashima , Crystal D. Rogers","doi":"10.1016/j.diff.2025.100856","DOIUrl":"10.1016/j.diff.2025.100856","url":null,"abstract":"<div><div>Embryonic exposures to non-steroidal anti-inflammatory drugs (NSAIDs) have been linked to preterm birth, neural tube closure defects, abnormal enteric innervation, and craniofacial malformations, potentially due to disrupted neural tube or neural crest (NC) cell development. Naproxen (NPX), a common non-steroidal anti-inflammatory drug (NSAID) used to relieve pain and inflammation, exerts its effects through non-selective cyclooxygenase (COX) inhibition. Our lab has identified that the cyclooxygenase (COX-1 and COX-2) isoenzymes are expressed during the early stages of vertebrate embryonic development, and that global inhibition of COX-1 and COX-2 function disrupts NC cell migration and differentiation in <em>Ambystoma mexicanum</em> (axolotl) embryos. NC cells differentiate into various adult tissues including craniofacial cartilage, bone, and neurons in the peripheral and enteric nervous systems. To investigate the specific phenotypic and molecular effects of NPX exposure on NC development and differentiation, and to identify molecular links between COX inhibition and NC derivative anomalies, we exposed late neurula and early tailbud stage axolotl embryos to various concentrations of NPX and performed immunohistochemistry (IHC) for markers of migratory and differentiating NC cells. Our results reveal that NPX exposure impairs the migration of SOX9+ NC cells, leading to abnormal development of craniofacial cartilage structures, including Meckel’s cartilage in the jaw. NPX exposure also alters the expression of markers associated with peripheral and central nervous system (PNS and CNS) development, suggesting concurrent neurodevelopmental changes.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"143 ","pages":"Article 100856"},"PeriodicalIF":2.2,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143715000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

WNT9A and WNT9B in Development and Disease WNT9A和WNT9B在发育和疾病中的作用。

IF 2.2 3区生物学

Differentiation Pub Date : 2025-03-01 DOI: 10.1016/j.diff.2024.100820

Amber D. Ide, Stephanie Grainger

引用次数: 0

Delamination of chick cephalic neural crest cells requires an MMP14-dependent downregulation of Cadherin-6B 鸡头神经嵴细胞分层需要mmp14依赖性下调钙粘蛋白6b。

IF 2.2 3区生物学

Differentiation Pub Date : 2025-03-01 DOI: 10.1016/j.diff.2025.100836

Cyril Andrieu , Cathy Danesin , Audrey Montigny , Marie Rey , Klara Baqué , Anne Bibonne , Dominique Alfandari , Eric Theveneau

{"title":"Delamination of chick cephalic neural crest cells requires an MMP14-dependent downregulation of Cadherin-6B","authors":"Cyril Andrieu , Cathy Danesin , Audrey Montigny , Marie Rey , Klara Baqué , Anne Bibonne , Dominique Alfandari , Eric Theveneau","doi":"10.1016/j.diff.2025.100836","DOIUrl":"10.1016/j.diff.2025.100836","url":null,"abstract":"<div><div>Matrix Metalloproteinases (MMPs) are known for their role in matrix remodeling via their catalytic activities in the extracellular space. Interestingly, these enzymes can also play less expected roles in cell survival, polarity and motility via other substrates (e.g. receptors, chemokines), through an intracellular localization (e.g. the nucleus) or via non-catalytic functions. Most of these unconventional functions are yet to be functionally validated in a physiological context. Here, we used the delamination of the cephalic Neural Crest (NC) cells of the chicken embryo, a well described experimental model of epithelial-mesenchymal transition (EMT), to study the <em>in vivo</em> function of MMP14 (a.k.a MT1-MMP). MMP14 is a transmembrane MMP known for its importance in cell invasion and often associated with poor prognosis in cancer. We found that MMP14 is expressed and required for cephalic NC delamination. More specifically, MMP14 is necessary for the downregulation of Cadherin-6B and a co-inhibition of Cadherin-6B and MMP14 expressions is sufficient to restore NC delamination. Cadherin-6B is normally repressed by Snail2. Surprisingly, in MMP14 knockdown this lack of Cadherin-6B repression occurs in the context of a normal expression and nuclear import of Snail2. We further show that MMP14 is not detected in the nucleus and that Snail2 and MMP14 do not physically interact. These data reveals that a yet to be identified MMP14-dependent signaling event is required for the Snail2-dependent repression of Cadherin-6B. In conclusion, this work provides an <em>in vivo</em> example of atypical regulation of Cadherins by an MMP which emphasizes the importance and diversity of non-canonical functions of MMPs.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"142 ","pages":"Article 100836"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The primary cilia: Orchestrating cranial neural crest cell development 初级纤毛协调颅神经嵴细胞的发育

IF 2.2 3区生物学

Differentiation Pub Date : 2025-03-01 DOI: 10.1016/j.diff.2024.100818

Hiroyuki Yamaguchi , Matthew D. Meyer , William B. Barrell , Maryam Faisal , Rebecca Berdeaux , Karen J. Liu , Yoshihiro Komatsu

引用次数: 0