为什么细胞应激会抑制骨骼组织中的脂肪生成，但在脂肪组织中无效：通过细胞外基质中的整合素结合位点控制间充质细胞分化。
Why cellular stress suppresses adipogenesis in skeletal tissue, but is ineffective in adipose tissue: control of mesenchymal cell differentiation via integrin binding sites in extracellular matrices.
机构信息
Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA, USA.
出版信息
Matrix Biol. 2013 Oct-Nov;32(7-8):365-71. doi: 10.1016/j.matbio.2013.06.001. Epub 2013 Jun 18.
Abstract
This Perspective addresses one of the major puzzles of adipogenesis in adipose tissue, namely its resistance to cellular stress. It introduces a concept of "density" of integrin binding sites in extracellular matrix, proposes a cellular signaling explanation for the observed effects of matrix elasticity and of cell shape on mesenchymal stem cell differentiation, and discusses how specialized integrin binding sites in collagen IV-containing matrices guard two pivotal physiological and evolutionary processes: stress-resistant adipogenesis in adipose tissues and preservation of pluripotency of mesenchymal stem-like cells in their storage niches. Finally, it proposes strategies to suppress adipogenesis in adipose tissues.
摘要
这篇观点文章探讨了脂肪组织中脂肪生成对细胞应激的抗性这一主要难题之一。它介绍了细胞外基质中整合素结合位点“密度”的概念，提出了细胞信号转导解释，以说明基质弹性和细胞形状对间充质干细胞分化的观察到的影响，并讨论了富含胶原 IV 的基质中的特殊整合素结合位点如何保护两个关键的生理和进化过程：脂肪组织中抗应激性脂肪生成和间充质干细胞样细胞在其储存龛中的多能性的保存。最后，它提出了抑制脂肪组织中脂肪生成的策略。
相似文献
1
Why cellular stress suppresses adipogenesis in skeletal tissue, but is ineffective in adipose tissue: control of mesenchymal cell differentiation via integrin binding sites in extracellular matrices.为什么细胞应激会抑制骨骼组织中的脂肪生成，但在脂肪组织中无效：通过细胞外基质中的整合素结合位点控制间充质细胞分化。
Matrix Biol. 2013 Oct-Nov;32(7-8):365-71. doi: 10.1016/j.matbio.2013.06.001. Epub 2013 Jun 18.
2
Matrix directed adipogenesis and neurogenesis of mesenchymal stem cells derived from adipose tissue and bone marrow.基质导向脂肪组织和骨髓来源的间充质干细胞的脂肪生成和神经生成。
Acta Biomater. 2016 Sep 15;42:46-55. doi: 10.1016/j.actbio.2016.06.037. Epub 2016 Jun 29.
3
Characterization of cell signaling, morphology, and differentiation potential of human mesenchymal stem cells based on cell adhesion mechanism.基于细胞黏附机制的人骨髓间充质干细胞的细胞信号转导、形态和分化潜能的表征。
J Cell Physiol. 2020 Oct;235(10):6915-6928. doi: 10.1002/jcp.29587. Epub 2020 Feb 4.
4
Collagen I matrix contributes to determination of adult human stem cell lineage via differential, structural conformation-specific elicitation of cellular stress response.I型胶原蛋白基质通过对细胞应激反应的差异性、结构构象特异性诱导，有助于确定成人人类干细胞谱系。
Matrix Biol. 2009 Jun;28(5):251-62. doi: 10.1016/j.matbio.2009.04.002. Epub 2009 Apr 16.
5
Progression of human bone marrow stromal cells into both osteogenic and adipogenic lineages is differentially regulated by structural conformation of collagen I matrix via distinct signaling pathways.人骨髓基质细胞向成骨和成脂谱系的分化受到I型胶原基质结构构象通过不同信号通路的差异调节。
Matrix Biol. 2009 Jun;28(5):239-50. doi: 10.1016/j.matbio.2009.04.003. Epub 2009 Apr 16.
6
Regulating osteogenesis and adipogenesis in adipose-derived stem cells by controlling underlying substrate stiffness.通过控制潜在基质硬度来调节脂肪来源干细胞中的成骨和脂肪生成。
J Cell Physiol. 2018 Apr;233(4):3418-3428. doi: 10.1002/jcp.26193. Epub 2017 Nov 10.
7
Differential effect of myocardial matrix and integrins on cardiac differentiation of human mesenchymal stem cells.心肌基质和整合素对人骨髓间充质干细胞心脏分化的差异影响。
Differentiation. 2010 Apr-Jun;79(4-5):260-71. doi: 10.1016/j.diff.2010.02.005. Epub 2010 Mar 21.
8
The balance of osteogenic and adipogenic differentiation in human mesenchymal stem cells by matrices that mimic stepwise tissue development.通过模仿组织逐步发育的基质来实现人骨髓间充质干细胞的成骨和成脂分化平衡。
Biomaterials. 2012 Mar;33(7):2025-31. doi: 10.1016/j.biomaterials.2011.11.061. Epub 2011 Dec 15.
9
Hematopoietic-to-mesenchymal transition of adipose tissue macrophages is regulated by integrin β1 and fabricated fibrin matrices.脂肪组织巨噬细胞的造血向间充质转变受整合素β1和人工合成纤维蛋白基质的调控。
Adipocyte. 2017 Jul 3;6(3):234-249. doi: 10.1080/21623945.2017.1314403. Epub 2017 Apr 3.
10
Space microgravity drives transdifferentiation of human bone marrow-derived mesenchymal stem cells from osteogenesis to adipogenesis.空间微重力促使人类骨髓间充质干细胞从成骨向成脂分化。
FASEB J. 2018 Aug;32(8):4444-4458. doi: 10.1096/fj.201700208RR. Epub 2018 Mar 13.
引用本文的文献
1
Serum insulin-like growth factor binding protein 2 is associated with hepatic steatosis in adults with metabolic dysfunction-associated steatotic liver disease.血清胰岛素样生长因子结合蛋白2与代谢功能障碍相关脂肪性肝病成人患者的肝脂肪变性有关。
Endocr Connect. 2025 Jul 17;14(7). doi: 10.1530/EC-25-0285. Print 2025 Jul 1.
2
Extracellular Vesicles Derived from Osteogenic-Differentiated Human Bone Marrow-Derived Mesenchymal Cells Rescue Osteogenic Ability of Bone Marrow-Derived Mesenchymal Cells Impaired by Hypoxia.源自成骨分化的人骨髓间充质细胞的细胞外囊泡可挽救受缺氧损伤的骨髓间充质细胞的成骨能力。
Biomedicines. 2023 Oct 16;11(10):2804. doi: 10.3390/biomedicines11102804.
3
The Characterization and Differential Analysis of mA Methylation in Hycole Rabbit Muscle and Adipose Tissue and Prediction of Regulatory Mechanism about Intramuscular Fat.海科兔肌肉和脂肪组织中 mA 甲基化的表征与差异分析及肌内脂肪调控机制预测
Animals (Basel). 2023 Jan 28;13(3):446. doi: 10.3390/ani13030446.
4
Potential Role of Insulin Growth-Factor-Binding Protein 2 as Therapeutic Target for Obesity-Related Insulin Resistance.胰岛素生长因子结合蛋白 2 作为肥胖相关胰岛素抵抗治疗靶点的潜在作用。
Int J Mol Sci. 2021 Jan 24;22(3):1133. doi: 10.3390/ijms22031133.
5
Hybrid Synthetic-Biological Hydrogel System for Adipose Tissue Regeneration.用于脂肪组织再生的杂交合成-生物水凝胶系统。
Macromol Biosci. 2018 Nov;18(11):e1800122. doi: 10.1002/mabi.201800122. Epub 2018 Sep 24.
6
Down regulation of ITGA4 and ITGA5 genes after formation of 3D spherules by human Wharton's jelly stem cells (hWJSCs).人脐带华通氏胶间充质干细胞（hWJSCs）形成三维球体后ITGA4和ITGA5基因的下调。
Mol Biol Rep. 2018 Jun;45(3):245-252. doi: 10.1007/s11033-018-4157-0. Epub 2018 Feb 6.
7
Transcriptome analysis and identification of significantly differentially expressed genes in Holstein calves subjected to severe thermal stress.牛犊在遭受严重热应激时的转录组分析及差异表达基因鉴定。
Int J Biometeorol. 2017 Nov;61(11):1993-2008. doi: 10.1007/s00484-017-1392-3. Epub 2017 Sep 12.
8
Hematopoietic-to-mesenchymal transition of adipose tissue macrophages is regulated by integrin β1 and fabricated fibrin matrices.脂肪组织巨噬细胞的造血向间充质转变受整合素β1和人工合成纤维蛋白基质的调控。
Adipocyte. 2017 Jul 3;6(3):234-249. doi: 10.1080/21623945.2017.1314403. Epub 2017 Apr 3.
9
The extracellular microscape governs mesenchymal stem cell fate.细胞外微环境决定间充质干细胞的命运。
J Biol Eng. 2016 Nov 21;10:16. doi: 10.1186/s13036-016-0037-0. eCollection 2016.
10
The miR-181d-regulated metalloproteinase Adamts1 enzymatically impairs adipogenesis via ECM remodeling.受miR-181d调控的金属蛋白酶Adamts1通过细胞外基质重塑对脂肪生成产生酶促损伤作用。
Cell Death Differ. 2016 Nov 1;23(11):1778-1791. doi: 10.1038/cdd.2016.66. Epub 2016 Jul 22.
本文引用的文献
1
METABOLIC FUNCTIONS OF MYOSTATIN AND GDF11.肌肉生长抑制素和生长分化因子11的代谢功能
Immunol Endocr Metab Agents Med Chem. 2010 Dec;10(4):217-231. doi: 10.2174/187152210793663810.
2
Matrix remodeling as stem cell recruitment event: a novel in vitro model for homing of human bone marrow stromal cells to the site of injury shows crucial role of extracellular collagen matrix.基质重构作为干细胞募集事件：一种新的体外模型用于研究人骨髓基质细胞归巢到损伤部位，显示细胞外胶原基质的关键作用。
Matrix Biol. 2010 Oct;29(8):657-63. doi: 10.1016/j.matbio.2010.08.008. Epub 2010 Sep 7.
3
Adult human bone marrow stromal cells regulate expression of their MMPs and TIMPs in differentiation type-specific manner.成体人骨髓基质细胞以分化类型特异性方式调节其 MMPs 和 TIMPs 的表达。
Matrix Biol. 2010 Jan;29(1):3-8. doi: 10.1016/j.matbio.2009.09.003. Epub 2009 Sep 17.
4
Human bone marrow-derived stromal cells show highly efficient stress-resistant adipogenesis on denatured collagen IV matrix but not on its native counterpart: implications for obesity.人骨髓基质细胞在变性胶原 IV 基质上表现出高效的抗应激成脂作用，但不在其天然对应物上：对肥胖的影响。
Matrix Biol. 2010 Jan;29(1):9-14. doi: 10.1016/j.matbio.2009.09.002. Epub 2009 Sep 15.
5
The effects of a soluble activin type IIB receptor on obesity and insulin sensitivity.可溶性激活素 IIB 型受体对肥胖和胰岛素敏感性的影响。
Int J Obes (Lond). 2009 Nov;33(11):1265-73. doi: 10.1038/ijo.2009.162. Epub 2009 Aug 11.
6
Collagen I matrix contributes to determination of adult human stem cell lineage via differential, structural conformation-specific elicitation of cellular stress response.I型胶原蛋白基质通过对细胞应激反应的差异性、结构构象特异性诱导，有助于确定成人人类干细胞谱系。
Matrix Biol. 2009 Jun;28(5):251-62. doi: 10.1016/j.matbio.2009.04.002. Epub 2009 Apr 16.
7
Progression of human bone marrow stromal cells into both osteogenic and adipogenic lineages is differentially regulated by structural conformation of collagen I matrix via distinct signaling pathways.人骨髓基质细胞向成骨和成脂谱系的分化受到I型胶原基质结构构象通过不同信号通路的差异调节。
Matrix Biol. 2009 Jun;28(5):239-50. doi: 10.1016/j.matbio.2009.04.003. Epub 2009 Apr 16.
8
Myostatin inhibition in muscle, but not adipose tissue, decreases fat mass and improves insulin sensitivity.肌肉而非脂肪组织中的肌生成抑制素抑制作用可减少脂肪量并改善胰岛素敏感性。
PLoS One. 2009;4(3):e4937. doi: 10.1371/journal.pone.0004937. Epub 2009 Mar 19.
9
Glycogen synthase kinase 3beta (GSK3beta) in tumorigenesis and cancer chemotherapy.糖原合酶激酶3β（GSK3β）在肿瘤发生及癌症化疗中的作用
Cancer Lett. 2009 Jan 18;273(2):194-200. doi: 10.1016/j.canlet.2008.05.045. Epub 2008 Jul 7.
10
Myostatin, activin receptor IIb, and follistatin-like-3 gene expression are altered in adipose tissue and skeletal muscle of obese mice.在肥胖小鼠的脂肪组织和骨骼肌中，肌生成抑制素、激活素受体IIb和类卵泡抑素-3基因表达发生改变。
Am J Physiol Endocrinol Metab. 2008 May;294(5):E918-27. doi: 10.1152/ajpendo.00798.2007. Epub 2008 Mar 11.
Zotero 插件