scholarly journals Multiple roles of syndecan-4 during myoblast migration

2021 ◽  
Author(s):  
Dániel Becsky
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Cell Migration ◽  
Embryonic Development ◽  
Cell Polarity ◽  
Focal Adhesion ◽  
Muscle Disease ◽  
Satellite Stem Cells ◽  
Migrating Cells

Background and purpose: Cell migration is one of the cornerstones of regeneration processes, as it is necessary for wound healing, and also required for embryonic development, immune system activation, or tumor metastasis formation. Skeletal muscle has a special, advanced dynamism that allows it to adapt to various impacts and recover successfully after an injury, exercise, or muscle disease. Satellite stem cells are activated by local damage during muscle regeneration, and after asymmetric division, myoblasts (i.e., activated satellite cells) migrate to the site of injury, differentiate, and fuse to form muscle fibers. Migration of the cells requires cellular polarization, the creation of leading and trailing edges, as well as the proper orientation and positioning of organelles inside the cell. Efficient migration also requires the presence of an asymmetrical front-to-rear calcium (Ca2+) gradient to regulate focal adhesion assembly and actomyosin contractility. The transmembrane proteoglycan syndecan-4 (SDC4), which is one of the cell surface markers of resting and activated satellite stem cells, is involved in the formation of focal adhesions. Furthermore, SDC4 plays a variety of roles in signal transduction processes, including controlling the function of the small GTPase Rac1 by binding to and inhibiting the activity of T-lymphoma invasion and metastasis-1 (Tiam1), a guanine nucleotide exchange factor for Rac1 (Ras-related C3 botulinum toxin substrate 1) GTPase. Cell migration also requires Rac1-mediated actin remodeling. SDC4 knockout mice are unable to regenerate damaged muscle; however, its underlying precise mechanism is unclear; therefore, our aim was to analyze the role of SDC4 in myoblast migration. Experimental approaches: To achieve SDC4 knockdown, C2C12 murine myoblast cells were transfected stably with plasmids expressing short hairpin RNAs (shRNAs) specific for mouse SDC4 (shSDC4#1 and shSDC4#2) or a scrambled target sequence. To study cell migration, time-lapse images were captured at 37 °C and 5% CO2 using a high-content imaging system for single-cell tracking or wound scratch assay was performed. To evaluate the movement of the single cells, the cell nuclei were tracked with ImageJ and CellTracker software. Super-resolution direct stochastic optical reconstruction microscopy (dSTORM) measurements were performed for the nanoscale analysis of the lamellipodial actin network of the migrating cells. To study the intracellular Ca2+ level, Fluo-4 and Fura Red indicators were applied. Immunofluorescence cytochemistry was performed to analyze the distribution of SDC4, Tiam1, centrosomes, FAK (focal adhesion kinase) or GM130 (anti- Golgi matrix protein of 130 kDa) followed by wide-field fluorescence or confocal microscopy. Image analysis was performed with ImageJ. Rac1 was inhibited by NSC23766 treatment during the measurements (50 µM). Key results: Silencing of SDC4 disrupts the correct polarization of migrating mammalian myoblasts. SDC4 knockdown completely abolished the intracellular Ca2+ gradient, abrogated centrosome reorientation, and thus decreased cell motility, demonstrating the role of SDC4 in cell polarity. Additionally, SDC4 exhibited a polarized distribution during migration. SDC4 knockdown cells exhibited decreases in the total movement distance during migration, maximum and vectorial distances from the starting point, as well as average and maximum cell speeds. Analysis of the dSTORM images of SDC4 knockdown cells revealed nanoscale changes in the actin cytoskeletal architecture, such as decreases in the numbers of branches and individual branch lengths in the lamellipodia of the migrating cells. The Rac1 inhibitor NSC23766 did not restore the migration capacity of SDC4 silenced cells; in fact, it reduced it further. SDC4 knockdown decreased the directional persistence of migration, abrogated the polarized, asymmetric distribution of Tiam1, and reduced the total Tiam1 level of the cells. Conclusion: According to our results, SDC4 affects the migration of C2C12 myoblasts and modulates cell polarity by influencing centrosome positioning, intracellular Ca2+ and Tiam1 distribution. These findings may promote greater understanding the essential role of SDC4 in the embryonic development and postnatal regeneration of skeletal muscle. Given the ubiquitous expression and crucial role of SDC4 in cell migration, we conclude that our findings can facilitate understanding the general role of SDC4 during cell migration.

scholarly journals Dietary Patterns, Skeletal Muscle Health, and Sarcopenia in Older Adults

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 745 ◽  
Author(s):  
Antoneta Granic ◽  
Avan Sayer ◽  
Sian Robinson
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Dietary Patterns ◽  
Healthy Eating Index ◽  
Muscle Disease ◽  
Nutritional Epidemiology ◽  
Societal Implications ◽  
Increased Risk ◽  
Muscle Health

In recent decades, the significance of diet and dietary patterns (DPs) for skeletal muscle health has been gaining attention in ageing and nutritional research. Sarcopenia, a muscle disease characterised by low muscle strength, mass, and function is associated with an increased risk of functional decline, frailty, hospitalization, and death. The prevalence of sarcopenia increases with age and leads to high personal, social, and economic costs. Finding adequate nutritional measures to maintain muscle health, preserve function, and independence for the growing population of older adults would have important scientific and societal implications. Two main approaches have been employed to study the role of diet/DPs as a modifiable lifestyle factor in sarcopenia. An a priori or hypothesis-driven approach examines the adherence to pre-defined dietary indices such as the Mediterranean diet (MED) and Healthy Eating Index (HEI)—measures of diet quality—in relation to muscle health outcomes. A posteriori or data-driven approaches have used statistical tools—dimension reduction methods or clustering—to study DP-muscle health relationships. Both approaches recognise the importance of the whole diet and potential cumulative, synergistic, and antagonistic effects of foods and nutrients on ageing muscle. In this review, we have aimed to (i) summarise nutritional epidemiology evidence from four recent systematic reviews with updates from new primary studies about the role of DPs in muscle health, sarcopenia, and its components; (ii) hypothesise about the potential mechanisms of ‘myoprotective’ diets, with the MED as an example, and (iii) discuss the challenges facing nutritional epidemiology to produce the higher level evidence needed to understand the relationships between whole diets and healthy muscle ageing.

scholarly journals Insulin-Like Growth Factor Binding Protein-6 Promotes the Differentiation of Placental Mesenchymal Stem Cells into Skeletal Muscle Independent of Insulin-Like Growth Factor Receptor-1 and Insulin Receptor

2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
Doaa Aboalola ◽  
Victor K. M. Han
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Muscle Differentiation ◽  
Insulin Like Growth Factor ◽  
Differentiation Process ◽  
Placental Mesenchymal Stem Cells

As mesenchymal stem cells (MSCs) are being investigated for regenerative therapies to be used in the clinic, delineating the roles of the IGF system in MSC growth and differentiation, in vitro, is vital in developing these cellular therapies to treat degenerative diseases. Muscle differentiation is a multistep process, starting with commitment to the muscle lineage and ending with the formation of multinucleated fibers. Insulin-like growth factor binding protein-6 (IGFBP-6), relative to other IGFBPs, has high affinity for IGF-2. However, the role of IGFBP-6 in muscle development has not been clearly defined. Our previous studies showed that in vitro extracellular IGFBP-6 increased myogenesis in early stages and could enhance the muscle differentiation process in the absence of IGF-2. In this study, we identified the signal transduction mechanisms of IGFBP-6 on muscle differentiation by placental mesenchymal stem cells (PMSCs). We showed that muscle differentiation required activation of both AKT and MAPK pathways. Interestingly, we demonstrated that IGFBP-6 could compensate for IGF-2 loss and help enhance the muscle differentiation process by triggering predominantly the MAPK pathway independent of activating either IGF-1R or the insulin receptor (IR). These findings indicate the complex interactions between IGFBP-6 and IGFs in PMSC differentiation into the skeletal muscle and that the IGF signaling axis, specifically involving IGFBP-6, is important in muscle differentiation. Moreover, although the major role of IGFBP-6 is IGF-2 inhibition, it is not necessarily the case that IGFBP-6 is the main modulator of IGF-2.

The Role of Dystroglycan and Its Ligands in Physiology and Disease

Physiology ◽  
2000 ◽  
Vol 15 (5) ◽  
pp. 255-259 ◽  
Author(s):  
Thomas Meier ◽  
Markus A. Ruegg
Keyword(s):  
Extracellular Matrix ◽  
Cell Membrane ◽  
Basement Membrane ◽  
Embryonic Development ◽  
Bacterial Pathogens ◽  
Membrane Integrity ◽  
Muscle Disease ◽  
Entry Point ◽  
Cell Membrane Integrity

Dystroglycan contributes to the formation of basement membrane during embryonic development and enforces cell membrane integrity by bridging cytoskeleton and components of the extracellular matrix. In several forms of muscle disease, dystroglycan is reduced in abundance. Moreover, human viral and bacterial pathogens use dystroglycan as their cellular entry point.

Skeletal muscle satellite stem cells at different postmortem intervals

2016 ◽  
Vol 24 (1) ◽  
pp. 23-27
Author(s):  
Mihai Ceausu ◽  
Sorin Hostiuc ◽  
Dan Dermengiu
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Satellite Stem Cells

scholarly journals Stem cells for skeletal muscle repair

2011 ◽  
Vol 366 (1575) ◽  
pp. 2297-2306 ◽  
Author(s):  
Jennifer L. Shadrach ◽  
Amy J. Wagers
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Cell Function ◽  
Therapeutic Potential ◽  
Muscle Disease ◽  
Muscle Fibres ◽  
Muscle Repair ◽  
Muscle Satellite Cells

Skeletal muscle is a highly specialized tissue composed of non-dividing, multi-nucleated muscle fibres that contract to generate force in a controlled and directed manner. Skeletal muscle is formed during embryogenesis from a subset of muscle precursor cells, which generate both differentiated muscle fibres and specialized muscle-forming stem cells known as satellite cells. Satellite cells remain associated with muscle fibres after birth and are responsible for muscle growth and repair throughout life. Failure in satellite cell function can lead to delayed, impaired or failed recovery after muscle injury, and such failures become increasingly prominent in cases of progressive muscle disease and in old age. Recent progress in the isolation of muscle satellite cells and elucidation of the cellular and molecular mediators controlling their activity indicate that these cells represent promising therapeutic targets. Such satellite cell-based therapies may involve either direct cell replacement or development of drugs that enhance endogenous muscle repair mechanisms. Here, we discuss recent breakthroughs in understanding both the cell intrinsic and extrinsic regulators that determine the formation and function of muscle satellite cells, as well as promising paths forward to realizing their full therapeutic potential.

scholarly journals Transcriptional landscape of myogenesis from human pluripotent stem cells reveals a key role of TWIST1 in maintenance of skeletal muscle progenitors

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
In Young Choi ◽  
Hotae Lim ◽  
Hyeon Jin Cho ◽  
Yohan Oh ◽  
Bin-Kuan Chou ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Progenitor Cells ◽  
Pluripotent Stem Cells ◽  
Expression Profiles ◽  
Human Pluripotent Stem Cells ◽  
Knock Out ◽  
Muscle Progenitor Cells ◽  
Transcriptional Landscape

Generation of skeletal muscle cells with human pluripotent stem cells (hPSCs) opens new avenues for deciphering essential, but poorly understood aspects of transcriptional regulation in human myogenic specification. In this study, we characterized the transcriptional landscape of distinct human myogenic stages, including OCT4::EGFP+ pluripotent stem cells, MSGN1::EGFP+ presomite cells, PAX7::EGFP+ skeletal muscle progenitor cells, MYOG::EGFP+ myoblasts, and multinucleated myotubes. We defined signature gene expression profiles from each isolated cell population with unbiased clustering analysis, which provided unique insights into the transcriptional dynamics of human myogenesis from undifferentiated hPSCs to fully differentiated myotubes. Using a knock-out strategy, we identified TWIST1 as a critical factor in maintenance of human PAX7::EGFP+ putative skeletal muscle progenitor cells. Our data revealed a new role of TWIST1 in human skeletal muscle progenitors, and we have established a foundation to identify transcriptional regulations of human myogenic ontogeny (online database can be accessed in http://www.myogenesis.net/).

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