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Biomolecules
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Extracellular Factors of Connective Tissues: Regulation of Cell Fate and...
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Extracellular Factors of Connective Tissues: Regulation of Cell Fate and Disease Modelling Perspectives

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Cellular Biochemistry".

Deadline for manuscript submissions: closed (15 April 2023) | Viewed by 9639

Special Issue Editors

Dr. Zoran Ivanovic

E-Mail Website
Guest Editor
1. Etablissement Français du Sang Nouvelle Aquitaine, Place Amélie Raba Léon, CS22010, CEDEX, 33075 Bordeaux, France
2. Inserm Bordeaux UMR 1035, 33000 Bordeaux, France
3. Department of Biological and Medical Sciences, Campus Carreire, University of Bordeaux, 33000 Bordeaux, France
Interests: somatic stem cells; self-renewal; metabolic profile and stemness; anaerobiosis and stemness; ex vivo cell engineering
Special Issues, Collections and Topics in MDPI journals
Dr. Drenka Trivanovic

E-Mail Website
Guest Editor
Group for Hematology and Stem Cells, Institute for Medical Research, National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
Interests: stem cells; bone marrow adipose tissue; cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The family of connective tissue includes cartilage, bone, fat, blood and lymphatic tissue which participate in structural support and securing vital molecules storage and delivery for other tissues. The response of resident cells to environmental cues to maintain the mechanical properties of the extracellular matrix (ECM) and tissue integrity are fundamental for connective tissue health. Tissue and context-specific ECM signaling participates in morphogenesis, tissue repair as well as disease progression. Extracellular stimuli such as biochemical signaling molecules as well as physical or mechanical cues initiate various intracellular pathways leading to changes in the control of main cellular processes (i.e., differentiation, mobilization). Unraveling the molecular-, cellular-, and tissue-scale effects of extracellular signals should identify key molecular targets for the protection of healthy connective tissues, as well as treatments of injured or diseased connective tissues. In this Special Issue, we aim to collect novel knowledge on extracellular factors involved in the regulation of connective tissue states. Topics include, but are not limited to:

  • Versatility of connective tissue cells in homeostasis and disease;
  • Extracellular deposition of bioactive cell products in homeostasis and disease;
  • Extracellular matrix components: biochemical and mechanical signaling;
  • Extracellular vesicles as biomarkers and cell response regulators;
  • Harnessing extracellular bioactive products in bioengineering and medicine.

Dr. Zoran Ivanovic
Dr. Drenka Trivanovic
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. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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

  • connective tissue
  • extracellular matrix
  • extracellular vesicles
  • regeneration
  • injury

Published Papers (4 papers)

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Research

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19 pages, 8203 KiB  
Article
The Role of Doxycycline and IL-17 in Regenerative Potential of Periodontal Ligament Stem Cells: Implications in Periodontitis
by Ivana Okić Đorđević, Tamara Kukolj, Milena Živanović, Sanja Momčilović, Hristina Obradović, Anđelija Petrović, Slavko Mojsilović, Drenka Trivanović and Aleksandra Jauković
Biomolecules 2023, 13(10), 1437; https://doi.org/10.3390/biom13101437 - 24 Sep 2023
Viewed by 1012
Abstract
Periodontitis (PD) is a degenerative, bacteria-induced chronic disease of periodontium causing bone resorption and teeth loss. It includes a strong reaction of immune cells through the secretion of proinflammatory factors such as Interleukin-17 (IL-17). PD treatment may consider systemic oral antibiotics application, including [...] Read more.
Periodontitis (PD) is a degenerative, bacteria-induced chronic disease of periodontium causing bone resorption and teeth loss. It includes a strong reaction of immune cells through the secretion of proinflammatory factors such as Interleukin-17 (IL-17). PD treatment may consider systemic oral antibiotics application, including doxycycline (Dox), exhibiting antibacterial and anti-inflammatory properties along with supportive activity in wound healing, thus affecting alveolar bone metabolism. In the present study, we aimed to determine whether Dox can affect the regenerative potential of periodontal ligament mesenchymal stem cells (PDLSCs) modulated by IL-17 in terms of cell migration, osteogenic potential, bioenergetics and expression of extracellular matrix metalloproteinase 2 (MMP-2). Our findings indicate that Dox reduces the stimulatory effect of IL-17 on migration and MMP-2 expression in PDLSCs. Furthermore, Dox stimulates osteogenic differentiation of PDLSCs, annulling the inhibitory effect of IL-17 on PDLSCs osteogenesis. In addition, analyses of mitochondrial respiration reveal that Dox decreases oxygen consumption rate in PDLSCs exposed to IL-17, suggesting that changes in metabolic performance can be involved in Dox-mediated effects on PDLSCs. The pro-regenerative properties of Dox in inflammatory microenvironment candidates Dox in terms of regenerative therapy of PD-affected periodontium are observed. Full article
(This article belongs to the Special Issue Extracellular Factors of Connective Tissues: Regulation of Cell Fate and Disease Modelling Perspectives)
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13 pages, 2500 KiB  
Article
Using Microphysiological System for the Development of Treatments for Joint Inflammation and Associated Cartilage Loss—A Pilot Study
by Meagan J. Makarczyk, Sophie Hines, Haruyo Yagi, Zhong Alan Li, Alyssa M. Aguglia, Justin Zbikowski, Anne-Marie Padget, Qi Gao, Bruce A. Bunnell, Stuart B. Goodman and Hang Lin
Biomolecules 2023, 13(2), 384; https://doi.org/10.3390/biom13020384 - 17 Feb 2023
Cited by 5 | Viewed by 2706
Abstract
Osteoarthritis (OA) is a painful and disabling joint disease affecting millions worldwide. The lack of clinically relevant models limits our ability to predict therapeutic outcomes prior to clinical trials, where most drugs fail. Therefore, there is a need for a model that accurately [...] Read more.
Osteoarthritis (OA) is a painful and disabling joint disease affecting millions worldwide. The lack of clinically relevant models limits our ability to predict therapeutic outcomes prior to clinical trials, where most drugs fail. Therefore, there is a need for a model that accurately recapitulates the whole-joint disease nature of OA in humans. Emerging microphysiological systems provide a new opportunity. We recently established a miniature knee joint system, known as the miniJoint, in which human bone-marrow-derived mesenchymal stem cells (hBMSCs) were used to create an osteochondral complex, synovial-like fibrous tissue, and adipose tissue analogs. In this study, we explored the potential of the miniJoint in developing novel treatments for OA by testing the hypothesis that co-treatment with anti-inflammation and chondroinducing agents can suppress joint inflammation and associated cartilage degradation. Specifically, we created a “synovitis”-relevant OA model in the miniJoint by treating synovial-like tissues with interleukin-1β (IL-1β), and then a combined treatment of oligodeoxynucleotides (ODNs) suppressing the nuclear factor kappa beta (NF-κB) genetic pathway and bone morphogenic protein-7 (BMP-7) was introduced. The combined treatment with BMP-7 and ODNs reduced inflammation in the synovial-like fibrous tissue and showed an increase in glycosaminoglycan formation in the cartilage portion of the osteochondral complex. For the first time, this study demonstrated the potential of the miniJoint in developing disease-modifying OA drugs. The therapeutic efficacy of co-treatment with NF-κB ODNs and BMP-7 can be further validated in future clinical studies. Full article
(This article belongs to the Special Issue Extracellular Factors of Connective Tissues: Regulation of Cell Fate and Disease Modelling Perspectives)
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14 pages, 3766 KiB  
Article
Functional Loss of Terminal Complement Complex Protects Rabbits from Injury-Induced Osteoarthritis on Structural and Cellular Level
by Jana Riegger, Helga Joos, Valentin Möhler, Frank Leucht, Katrin Rading, Christian Kubisch, Anita Ignatius, Markus Huber-Lang and Rolf E. Brenner
Biomolecules 2023, 13(2), 216; https://doi.org/10.3390/biom13020216 - 22 Jan 2023
Cited by 1 | Viewed by 1484
Abstract
The terminal complement complex (TCC) has been described as a potential driver in the pathogenesis of posttraumatic osteoarthritis (PTOA). However, sublytic TCC deposition might also play a crucial role in bone development and regeneration. Therefore, we elucidated the effects of TCC on joint-related [...] Read more.
The terminal complement complex (TCC) has been described as a potential driver in the pathogenesis of posttraumatic osteoarthritis (PTOA). However, sublytic TCC deposition might also play a crucial role in bone development and regeneration. Therefore, we elucidated the effects of TCC on joint-related tissues using a rabbit PTOA model. In brief, a C6-deficient rabbit breed was characterized on genetic, protein, and functional levels. Anterior cruciate ligament transection (ACLT) was performed in C6-deficient (C6−/−) and C6-sufficient (C6+/−) rabbits. After eight weeks, the progression of PTOA was determined histologically. Moreover, the structure of the subchondral bone was evaluated by µCT analysis. C6 deficiency could be attributed to a homozygous 3.6 kb deletion within the C6 gene and subsequent loss of the C5b binding site. Serum from C6−/− animals revealed no hemolytic activity. After ACLT surgery, joints of C6−/− rabbits exhibited significantly lower OA scores, including reduced cartilage damage, hypocellularity, cluster formation, and osteophyte number, as well as lower chondrocyte apoptosis rates and synovial prostaglandin E2 levels. Moreover, ACLT surgery significantly decreased the trabecular number in the subchondral bone of C6−/− rabbits. Overall, the absence of TCC protected from injury-induced OA progression but had minor effects on the micro-structure of the subchondral bone. Full article
(This article belongs to the Special Issue Extracellular Factors of Connective Tissues: Regulation of Cell Fate and Disease Modelling Perspectives)
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Review

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20 pages, 1466 KiB  
Review
Extracellular Hemoglobin: Modulation of Cellular Functions and Pathophysiological Effects
by Ivana T. Drvenica, Ana Z. Stančić, Irina S. Maslovarić, Drenka I. Trivanović and Vesna Lj. Ilić
Biomolecules 2022, 12(11), 1708; https://doi.org/10.3390/biom12111708 - 17 Nov 2022
Cited by 8 | Viewed by 3693
Abstract
Hemoglobin is essential for maintaining cellular bioenergetic homeostasis through its ability to bind and transport oxygen to the tissues. Besides its ability to transport oxygen, hemoglobin within erythrocytes plays an important role in cellular signaling and modulation of the inflammatory response either directly [...] Read more.
Hemoglobin is essential for maintaining cellular bioenergetic homeostasis through its ability to bind and transport oxygen to the tissues. Besides its ability to transport oxygen, hemoglobin within erythrocytes plays an important role in cellular signaling and modulation of the inflammatory response either directly by binding gas molecules (NO, CO, and CO2) or indirectly by acting as their source. Once hemoglobin reaches the extracellular environment, it acquires several secondary functions affecting surrounding cells and tissues. By modulating the cell functions, this macromolecule becomes involved in the etiology and pathophysiology of various diseases. The up-to-date results disclose the impact of extracellular hemoglobin on (i) redox status, (ii) inflammatory state of cells, (iii) proliferation and chemotaxis, (iv) mitochondrial dynamic, (v) chemoresistance and (vi) differentiation. This review pays special attention to applied biomedical research and the use of non-vertebrate and vertebrate extracellular hemoglobin as a promising candidate for hemoglobin-based oxygen carriers, as well as cell culture medium additive. Although recent experimental settings have some limitations, they provide additional insight into the modulatory activity of extracellular hemoglobin in various cellular microenvironments, such as stem or tumor cells niches. Full article
(This article belongs to the Special Issue Extracellular Factors of Connective Tissues: Regulation of Cell Fate and Disease Modelling Perspectives)
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