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Cellular Mechanobiology: Mechanotransduction-Related Cell Signalling and Gene Expression
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Cellular Mechanobiology: Mechanotransduction-Related Cell Signalling and Gene Expression

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biophysics".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 10396

Special Issue Editors

Dr. Uwe Baumert

E-Mail Website
Guest Editor
Department of Orthodontics and Dentofacial Orthopedics, University Hospital, LMU Munich, 80336 Munich, Germany
Interests: cell mechanics; mechanobiology; molecular signalling; cell biology; in vitro cell-mechanics models; genetics of the oro-facial region
Prof. Dr. Matthias Folwaczny

E-Mail Website
Guest Editor
Department of Conservative Dentistry and Periodontology, LMU Klinikum, LMU München, 80336 Munich, Germany
Interests: tissue regeneration, cell signaling, mechanobiology, cellular inflammatory reaction, immunogenetics

Special Issue Information

Dear Colleagues,

The relevance of functional mechanical loading for the development, shape, and homeostasis of the body, organs, and tissue is well established by a huge body of evidence. The absence of mechanical force and/or excessive overload result in a number of pathological conditions, diseases, and dysfunctions. Microscopically, mechanical cues thus also affect individual tissue cell’s cellular proliferation, differentiation, motility, regeneration, adaptation, and protein synthesis.

Generally, mechanical signaling in cells can be divided into four distinct phases: (1) the sensing or reception of a mechanical force, (2) its conversion to an internal signal via biochemical coupling, (3) signal transmission to its effector side, and (4) the specific cellular response to this signal. Due to the complexness of most tissues, in vitro cell models have been established to elucidate the effect of different mechanical forces (e.g., tension, compression, shear, hydrostatic pressure, vibration, fluid shear) on cells originating from various tissues, including osteoblasts, osteocytes, osteoclasts, periodontal ligament cells, chondrocytes, and stem cells as well as cell properties such as stiffness, age, and the genetic and epigenetic status, and also substrate characteristics modulate the cellular response to mechanical loading. Despite growing experimental evidence, the molecular regulation of cellular mechanics remains to be fully elucidated in order to improve clinical treatment strategies.

This Special Issue aims at expanding the current knowledge on cellular mechanotransduction and its impact on the cell response based on in vitro force application models simulating/mimicking physiological, therapeutic, and/or pathological conditions. Experimental studies and review articles are welcome for consideration. Since IJMS is a journal of molecular science, pure clinical studies will not be suitable for inclusion, but clinical submissions with biomolecular experiments are welcome.

Dr. Uwe Baumert
Prof. Dr. Matthias Folwaczny
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cellular mechanics
  • mechanotransduction
  • in vitro force application
  • gene expression
  • cell proliferation
  • cell differentiation
  • cell regeneration
  • dentistry, orthodontics
  • bone
  • cartilage
  • tendon

Published Papers (5 papers)

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Research

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19 pages, 4444 KiB  
Article
GDF15 Promotes the Osteogenic Cell Fate of Periodontal Ligament Fibroblasts, thus Affecting Their Mechanobiological Response
by Lukas Lösch, Albert Stemmler, Adrian Fischer, Julia Steinmetz, Lisa Schuldt, Christoph-Ludwig Hennig, Judit Symmank and Collin Jacobs
Int. J. Mol. Sci. 2023, 24(12), 10011; https://doi.org/10.3390/ijms241210011 - 11 Jun 2023
Cited by 2 | Viewed by 1679
Abstract
Periodontal ligament fibroblasts (PdLFs) exert important functions in oral tissue and bone remodeling following mechanical forces, which are specifically applied during orthodontic tooth movement (OTM). Located between the teeth and the alveolar bone, mechanical stress activates the mechanomodulatory functions of PdLFs including regulating [...] Read more.
Periodontal ligament fibroblasts (PdLFs) exert important functions in oral tissue and bone remodeling following mechanical forces, which are specifically applied during orthodontic tooth movement (OTM). Located between the teeth and the alveolar bone, mechanical stress activates the mechanomodulatory functions of PdLFs including regulating local inflammation and activating further bone-remodeling cells. Previous studies suggested growth differentiation factor 15 (GDF15) as an important pro-inflammatory regulator during the PdLF mechanoresponse. GDF15 exerts its effects through both intracrine signaling and receptor binding, possibly even in an autocrine manner. The extent to which PdLFs are susceptible to extracellular GDF15 has not yet been investigated. Thus, our study aims to examine the influence of GDF15 exposure on the cellular properties of PdLFs and their mechanoresponse, which seems particularly relevant regarding disease- and aging-associated elevated GDF15 serum levels. Therefore, in addition to investigating potential GDF15 receptors, we analyzed its impact on the proliferation, survival, senescence, and differentiation of human PdLFs, demonstrating a pro-osteogenic effect upon long-term stimulation. Furthermore, we observed altered force-related inflammation and impaired osteoclast differentiation. Overall, our data suggest a major impact of extracellular GDF15 on PdLF differentiation and their mechanoresponse. Full article
(This article belongs to the Special Issue Cellular Mechanobiology: Mechanotransduction-Related Cell Signalling and Gene Expression)
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16 pages, 2954 KiB  
Article
Activation of the Mechanosensitive Ion Channels Piezo1 and TRPV4 in Primary Human Healthy and Osteoarthritic Chondrocytes Exhibits Ion Channel Crosstalk and Modulates Gene Expression
by Bibiane Steinecker-Frohnwieser, Birgit Lohberger, Stefan Toegel, Reinhard Windhager, Veronika Glanz, Cornelia Kratschmann, Andreas Leithner and Lukas Weigl
Int. J. Mol. Sci. 2023, 24(9), 7868; https://doi.org/10.3390/ijms24097868 - 26 Apr 2023
Cited by 4 | Viewed by 2044
Abstract
Osteoarthritis (OA) is the most common degenerative joint disease causing pain and functional limitations. Physical activity as a clinically relevant, effective intervention alleviates pain and promotes joint function. In chondrocytes, perception and transmission of mechanical signals are controlled by mechanosensitive ion channels, whose [...] Read more.
Osteoarthritis (OA) is the most common degenerative joint disease causing pain and functional limitations. Physical activity as a clinically relevant, effective intervention alleviates pain and promotes joint function. In chondrocytes, perception and transmission of mechanical signals are controlled by mechanosensitive ion channels, whose dysfunction in OA chondrocytes is leading to disease progression. Signaling of mechanosensitive ion channels Piezo/TRPV4 was analyzed by Yoda1/GSK1016790A application and calcium-imaging of Fura-2-loaded chondrocytes. Expression analysis was determined by qPCR and immunofluorescence in healthy vs. OA chondrocytes. Chondrocytes were mechanically stimulated using the Flexcell™ technique. Yoda1 and GSK1016790A caused an increase in intracellular calcium [Ca2+]i for Yoda1, depending on extracellularly available Ca2+. When used concomitantly, the agonist applied first inhibited the effect of subsequent agonist application, indicating mutual interference between Piezo/TRPV4. Yoda1 increased the expression of metalloproteinases, bone-morphogenic protein, and interleukins in healthy and OA chondrocytes to a different extent. Flexcell™-induced changes in the expression of MMPs and ILs differed from changes induced by Yoda1. We conclude that Piezo1/TRPV4 communicate with each other, an interference that may be impaired in OA chondrocytes. It is important to consider that mechanical stimulation may have different effects on OA depending on its intensity. Full article
(This article belongs to the Special Issue Cellular Mechanobiology: Mechanotransduction-Related Cell Signalling and Gene Expression)
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19 pages, 12486 KiB  
Article
Chondroitin Sulfate-Tyramine-Based Hydrogels for Cartilage Tissue Repair
by Ilona Uzieliene, Daiva Bironaite, Jolita Pachaleva, Edvardas Bagdonas, Arkadij Sobolev, Wei-Bor Tsai, Giedrius Kvedaras and Eiva Bernotiene
Int. J. Mol. Sci. 2023, 24(4), 3451; https://doi.org/10.3390/ijms24043451 - 9 Feb 2023
Cited by 8 | Viewed by 2271
Abstract
The degradation of cartilage, due to trauma, mechanical load or diseases, results in abundant loss of extracellular matrix (ECM) integrity and development of osteoarthritis (OA). Chondroitin sulfate (CS) is a member of the highly sulfated glycosaminoglycans (GAGs) and a primary component of cartilage [...] Read more.
The degradation of cartilage, due to trauma, mechanical load or diseases, results in abundant loss of extracellular matrix (ECM) integrity and development of osteoarthritis (OA). Chondroitin sulfate (CS) is a member of the highly sulfated glycosaminoglycans (GAGs) and a primary component of cartilage tissue ECM. In this study, we aimed to investigate the effect of mechanical load on the chondrogenic differentiation of bone marrow mesenchymal stem cells (BM-MCSs) encapsulated into CS-tyramine-gelatin (CS-Tyr/Gel) hydrogel in order to evaluate the suitability of this composite for OA cartilage regeneration studies in vitro. The CS-Tyr/Gel/BM-MSCs composite showed excellent biointegration on cartilage explants. The applied mild mechanical load stimulated the chondrogenic differentiation of BM-MSCs in CS-Tyr/Gel hydrogel (immunohistochemical collagen II staining). However, the stronger mechanical load had a negative effect on the human OA cartilage explants evaluated by the higher release of ECM components, such as the cartilage oligomeric matrix protein (COMP) and GAGs, compared to the not-compressed explants. Finally, the application of the CS-Tyr/Gel/BM-MSCs composite on the top of the OA cartilage explants decreased the release of COMP and GAGs from the cartilage explants. Data suggest that the CS-Tyr/Gel/BM-MSCs composite can protect the OA cartilage explants from the damaging effects of external mechanical stimuli. Therefore, it can be used for investigation of OA cartilage regenerative potential and mechanisms under the mechanical load in vitro with further perspectives of therapeutic application in vivo. Full article
(This article belongs to the Special Issue Cellular Mechanobiology: Mechanotransduction-Related Cell Signalling and Gene Expression)
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19 pages, 2299 KiB  
Article
Compressed Prostate Cancer Cells Decrease Osteoclast Activity While Enhancing Osteoblast Activity In Vitro
by Victor J. B. van Santen, Behrouz Zandieh Doulabi, Cornelis M. Semeins, Jolanda M. A. Hogervorst, Cornelia Bratengeier and Astrid D. Bakker
Int. J. Mol. Sci. 2023, 24(1), 759; https://doi.org/10.3390/ijms24010759 - 1 Jan 2023
Viewed by 1958
Abstract
Once prostate cancer cells metastasize to bone, they perceive approximately 2 kPa compression. We hypothesize that 2 kPa compression stimulates the epithelial-to-mesenchymal transition (EMT) of prostate cancer cells and alters their production of paracrine signals to affect osteoclast and osteoblast behavior. Human DU145 [...] Read more.
Once prostate cancer cells metastasize to bone, they perceive approximately 2 kPa compression. We hypothesize that 2 kPa compression stimulates the epithelial-to-mesenchymal transition (EMT) of prostate cancer cells and alters their production of paracrine signals to affect osteoclast and osteoblast behavior. Human DU145 prostate cancer cells were subjected to 2 kPa compression for 2 days. Compression decreased expression of 2 epithelial genes, 5 out of 13 mesenchymal genes, and increased 2 mesenchymal genes by DU145 cells, as quantified by qPCR. Conditioned medium (CM) of DU145 cells was added to human monocytes that were stimulated to differentiate into osteoclasts for 21 days. CM from compressed DU145 cells decreased osteoclast resorptive activity by 38% but did not affect osteoclast size and number compared to CM from non-compressed cells. CM was also added to human adipose stromal cells, grown in osteogenic medium. CM of compressed DU145 cells increased bone nodule production (Alizarin Red) by osteoblasts from four out of six donors. Compression did not affect IL6 or TNF-α production by PC DU145 cells. Our data suggest that compression affects EMT-related gene expression in DU145 cells, and alters their production of paracrine signals to decrease osteoclast resorptive activity while increasing mineralization by osteoblasts is donor dependent. This observation gives further insight in the altered behavior of PC cells upon mechanical stimuli, which could provide novel leads for therapies, preventing bone metastases. Full article
(This article belongs to the Special Issue Cellular Mechanobiology: Mechanotransduction-Related Cell Signalling and Gene Expression)
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Review

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43 pages, 2171 KiB  
Review
On the Value of In Vitro Cell Systems for Mechanobiology from the Perspective of Yes-Associated Protein/Transcriptional Co-Activator with a PDZ-Binding Motif and Focal Adhesion Kinase and Their Involvement in Wound Healing, Cancer, Aging, and Senescence
by Thorsten Steinberg, Martin Philipp Dieterle, Imke Ramminger, Charlotte Klein, Julie Brossette, Ayman Husari and Pascal Tomakidi
Int. J. Mol. Sci. 2023, 24(16), 12677; https://doi.org/10.3390/ijms241612677 - 11 Aug 2023
Cited by 1 | Viewed by 1636
Abstract
Mechanobiology comprises how cells perceive different mechanical stimuli and integrate them into a process called mechanotransduction; therefore, the related mechanosignaling cascades are generally important for biomedical research. The ongoing discovery of key molecules and the subsequent elucidation of their roles in mechanobiology are [...] Read more.
Mechanobiology comprises how cells perceive different mechanical stimuli and integrate them into a process called mechanotransduction; therefore, the related mechanosignaling cascades are generally important for biomedical research. The ongoing discovery of key molecules and the subsequent elucidation of their roles in mechanobiology are fundamental to understanding cell responses and tissue conditions, such as homeostasis, aging, senescence, wound healing, and cancer. Regarding the available literature on these topics, it becomes abundantly clear that in vitro cell systems from different species and tissues have been and are extremely valuable tools for enabling the discovery and functional elucidation of key mechanobiological players. Therefore, this review aims to discuss the significant contributions of in vitro cell systems to the identification and characterization of three such key players using the selected examples of yes-associated protein (YAP), its paralog transcriptional co-activator with a PDZ-binding motif (TAZ), and focal adhesion kinase (FAK) and their involvement in wound healing, cancer, aging, and senescence. In addition, the reader is given suggestions as to which future prospects emerge from the in vitro studies discussed herein and which research questions still remain open. Full article
(This article belongs to the Special Issue Cellular Mechanobiology: Mechanotransduction-Related Cell Signalling and Gene Expression)
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