Actomyosin and the MRTF-SRF pathway downregulate FGFR1 in mesenchymal stromal cells

Zonderland, Jip; Rezzola, Silvia; Moroni, Lorenzo

doi:10.1038/s42003-020-01309-1

Cited by 5 publications

(3 citation statements)

References 64 publications

(83 reference statements)

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“…Fibroblasts maintain high SRF and FGFR1 expression and remain responsive to bFGF. (18) Fibroblasts produce endogenous bFGF which acts via autocrine mechanisms on FGFR1. Cultures using FBS contain exogenous and endogenous bFGF, as well as other growth factors, such as endothelial cell growth factor (ECGF), epidermal growth factor (EGF), fibroblast growth factor (FGF), insulin-like growth factor (IGF), nerve growth factor (NGF), plateletderived growth factor (PDGF), and transforming growth factor (TGF).…”

Section: Discussionmentioning

confidence: 99%

Comparative analysis of KnockOut serum replacement and fetal bovine serum for in vitro culture of human dermal fibroblasts

Hidayati,

Kusuma,

Poerwanto

2023

Univ Med

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BACKGROUNDHuman dermal fibroblast (HDF) cultures can be used as a regenerative agent for wound healing. Fetal bovine serum (FBS) as a culture supplement is derived from animals, therefore not being constant in composition, causes variations in research results, thus requiring a substitute such as KnockOut serum replacement (KOSR). This study evaluated the defined KOSR as FBS substitute for HDF culture by measuring the relative expression of basic fibroblast growth factor (bFGF) and keratinocyte growth factor (KGF) messenger RNA (mRNA), HDF cell proliferation, and HDF migration. METHODSHuman dermal fibroblast culture was divided into 2 intervention groups receiving KOSR 5% and KOSR 10%, respectively, and a control group receiving FBS 10%. Reverse transcription polymerase chain reaction (RT-PCR) was used for bFGF and KGF mRNA relative expression at the fifth passage (P5). Cell counting kit-8 (CCK-8) reagent was used for the HDF cell proliferation assay at P5 and the scratch assay was used for HDF cell migration at P6. Data were analyzed using dependent t-test, One-way ANOVA, or Kruskal-Wallis test. RESULTSThere were no significant differences in bFGF and KGF mRNA relative expression and HDF migration velocity between the intervention and control groups (p>0.05 and p>0.05, respectively). The doubling time of the KOSR 5% group showed no significant difference (p>0.05), but KOSR 10% and FBS 10% showed significant differences between treatment days 2-6 and treatment days 6-10 (p<0.05). CONCLUSIONSThe KOSR 10% was comparable to FBS 10% in supporting bFGF and KGF mRNA relative expression, HDF cell proliferation, and HDF cell migration in HDF culture.

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Section: Discussionmentioning

confidence: 99%

Comparative analysis of KnockOut serum replacement and fetal bovine serum for in vitro culture of human dermal fibroblasts

Hidayati,

Kusuma,

Poerwanto

2023

Univ Med

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“…For transcription factors, 𝑥 𝑖 refers to a transcriptionally eligible concentration, which includes the steady-state level of nuclear localization. Examples of transcription factors with wellknown stiff-correlated nuclear localization include YAP (35,36), MKL-1 (20,37), and RUNX2 (38,39); nuclear localization is necessary for transcription factor activity due to the possibility of co-activation requirements. We also include epigenetically modifying enzymes such as HDAC and HAT as elements of 𝑥 ⃗, which influence chromatin organization and demonstrate mechanosensitive activity patterns (8).…”

Section: Model For Dynamic Mechanosensitivity In the Cytoskeleton And The Nucleusmentioning

confidence: 99%

Dynamic Self-Reinforcement of Gene Expression Determines Acquisition and Retention of Cellular Mechanical Memory

Price

Mathur

et al. 2021

Preprint

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Mechanotransduction describes activation of gene expression by changes in the cell's physical microenvironment. Recent experiments show that mechanotransduction can lead to long-term "mechanical memory", where cells cultured on stiff substrates for sufficient time (priming phase) maintain altered phenotype after switching to soft substrates (dissipation phase), as compared to unprimed controls. The timescale of memory acquisition and retention is orders of magnitude larger than the timescale of mechanosensitive cellular signaling, and memory retention time changes continuously with priming time. We develop a model that captures these features by accounting for positive reinforcement in mechanical signaling. The sensitivity of reinforcement represents the dynamic transcriptional state of the cell composed of protein lifetimes and 3D chromatin organization. Our model provides a single framework connecting microenvironment mechanical history to cellular outcomes ranging from no memory to terminal differentiation. Predicting cellular memory of environmental changes can help engineer cellular dynamics through changes in culture environments.

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“…[33,34] In comparison, the use of polymer materials or hydrogels to release growth factors is often prone to loss of activity and dif ficulty for controlledrelease merely relying on hydrolysis. [35,36] As such, an ECM is considered to be a natural 3D mate rial that regulates the binding and release of growth factors, which can be leveraged to provide optimized biochemical cues during tissue morphogenesis. [37,38] Although bone morphoge netic protein2 (BMP2) has been used in clinic for over three decades, unfortunately its therapeutic index (the ratio of the maximal nontoxic system concentration to the minimal does elicit a positive therapeutic response) remains very low due to a number of factors such as poor solubility, short biological half life, unsatisfactory delivery materials, etc.…”

Section: Introductionmentioning

confidence: 99%

Vascular Derived ECM Improves Therapeutic Index of BMP‐2 and Drives Vascularized Bone Regeneration

Chen

Zhou

Sun

et al. 2022

Small

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Vascularized osteogenesis is essential for successful bone regeneration, yet its realization during large size bone defect healing remains challenging due to the difficulty to couple multiple biological processes. Herein, harnessing the intrinsic angiogenic potential of vascular derived extracellular matrix (vECM) and its specific affinity to growth factors, a vECM/GelMA based hybrid hydrogel delivery system is constructed to achieve optimized bone morphogenetic protein‐2 (BMP‐2) therapeutic index and provide intrinsic angiogenic induction during bone healing. The incorporation of vECM not only effectively regulates BMP‐2 kinetics to match the bone healing timeframe, but also promotes angiogenesis both in vitro and in vivo. In vivo results also show that vECM‐mediated BMP‐2 release remarkably enhances vascularized bone formation for critical size bone defects. In particular, blood vessel ingrowth stained with CD31 marker in the defect area is substantially encouraged over the course of healing, suggesting incorporation of vECM served roles in both angiogenesis and osteogenesis. Thus, the authors’ study exemplifies that affinity of growth factor towards ECM may be a promising strategy to be leveraged to develop sophisticated delivery systems endowed with desirable properties for regenerative medicine applications.

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Actomyosin and the MRTF-SRF pathway downregulate FGFR1 in mesenchymal stromal cells

Cited by 5 publications

References 64 publications

Comparative analysis of KnockOut serum replacement and fetal bovine serum for in vitro culture of human dermal fibroblasts

Comparative analysis of KnockOut serum replacement and fetal bovine serum for in vitro culture of human dermal fibroblasts

Dynamic Self-Reinforcement of Gene Expression Determines Acquisition and Retention of Cellular Mechanical Memory

Vascular Derived ECM Improves Therapeutic Index of BMP‐2 and Drives Vascularized Bone Regeneration

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