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Molecular Mechanisms of Cartilage Biology and Applications in Regenerative Medicine

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

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 8152

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Special Issue Editor

Dr. Piotr Dobrowolski

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Guest Editor

Department of Functional Anatomy and Cytobiology, Faculty of Biology and Biotechnology, Maria Curie-Sklodowska University, Akademicka 19, 20-033 Lublin, Poland
Interests: bone and cartilage histology; bone implants; cartilage regeneration; glutamine; alpha ketoglutaric acid; nutrients; supplementation; probiotics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue will consider articles that discuss all molecular aspects of cartilage biology, from development, differentiation, aging, injury, inflammatory diseases, natural regeneration, and the stimulation of regeneration with the help of surgical and drug therapy to nutritional supplementation. All aspects affecting cartilage metabolism, cell differentiation, and mechanical strength, reflected in the molecular, cellular, and histological structure and biochemical processes, will also be accepted.

Cartilage biology is a very broad term as with connective tissue in general. The more we know, the more detailed questions arise about many aspects of the various molecular processes taking place in cartilage. The development and mechanical endurance of arthritis-related malignancies, genetic disorders, and treatments for cartilage repairment as the holy grail of regenerative medicine, including medicines and dietary supplements. These are only examples of aspects where molecular mechanisms of cartilage biology are currently studied.

We hope this Special Issue will bring together high-quality papers that will expand the latest knowledge and create new pathways to an even deeper understanding of cartilage biology.

Dr. Piotr Dobrowolski
Guest Editor

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

articular cartilage
regeneration
differentiation
supplementation
metabolism
structure
development
arthritis
injury
treatment

Published Papers (6 papers)

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Research

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17 pages, 2471 KiB

Open AccessArticle

β1-Integrin-Mediated Uptake of Chondrocyte Extracellular Vesicles Regulates Chondrocyte Homeostasis

by Mohammed Tayab Hussain, Shani Austin-Williams, Thomas Dudley Wright, Umesh Kumar Dhawan, Andreia L. Pinto, Dianne Cooper and Lucy V. Norling

Int. J. Mol. Sci. 2024, 25(9), 4756; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25094756 - 26 Apr 2024

Viewed by 330

Abstract

Osteoarthritis (OA) is the most prevalent age-related degenerative disorder, which severely reduces the quality of life of those affected. Whilst management strategies exist, no cures are currently available. Virtually all joint resident cells generate extracellular vesicles (EVs), and alterations in chondrocyte EVs during OA have previously been reported. Herein, we investigated factors influencing chondrocyte EV release and the functional role that these EVs exhibit. Both 2D and 3D models of culturing C28I/2 chondrocytes were used for generating chondrocyte EVs. We assessed the effect of these EVs on chondrogenic gene expression as well as their uptake by chondrocytes. Collectively, the data demonstrated that chondrocyte EVs are sequestered within the cartilage ECM and that a bi-directional relationship exists between chondrocyte EV release and changes in chondrogenic differentiation. Finally, we demonstrated that the uptake of chondrocyte EVs is at least partially dependent on β1-integrin. These results indicate that chondrocyte EVs have an autocrine homeostatic role that maintains chondrocyte phenotype. How this role is perturbed under OA conditions remains the subject of future work. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Cartilage Biology and Applications in Regenerative Medicine)

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17 pages, 3911 KiB

Open AccessArticle

Inhibitory Effect of a Tankyrase Inhibitor on Mechanical Stress-Induced Protease Expression in Human Articular Chondrocytes

by Yoshifumi Hotta, Keiichiro Nishida, Aki Yoshida, Yoshihisa Nasu, Ryuichi Nakahara, Shuichi Naniwa, Noriyuki Shimizu, Chinatsu Ichikawa, Deting Lin, Tomohiro Fujiwara and Toshifumi Ozaki

Int. J. Mol. Sci. 2024, 25(3), 1443; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25031443 - 24 Jan 2024

Viewed by 817

Abstract

We investigated the effects of a Tankyrase (TNKS-1/2) inhibitor on mechanical stress-induced gene expression in human chondrocytes and examined TNKS-1/2 expression in human osteoarthritis (OA) cartilage. Cells were seeded onto stretch chambers and incubated with or without a TNKS-1/2 inhibitor (XAV939) for 12 h. Uni-axial cyclic tensile strain (CTS) (0.5 Hz, 8% elongation, 30 min) was applied and the gene expression of type II collagen a1 chain (COL2A1), aggrecan (ACAN), SRY-box9 (SOX9), TNKS-1/2, a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), and matrix metalloproteinase-13 (MMP-13) were examined by real-time PCR. The expression of ADAMTS-5, MMP-13, nuclear translocation of nuclear factor-κB (NF-κB), and β-catenin were examined by immunocytochemistry and Western blotting. The concentration of IL-1β in the supernatant was examined by enzyme-linked immunosorbent assay (ELISA). TNKS-1/2 expression was assessed by immunohistochemistry in human OA cartilage obtained at the total knee arthroplasty. TNKS-1/2 expression was increased after CTS. The expression of anabolic factors were decreased by CTS, however, these declines were abrogated by XAV939. XAV939 suppressed the CTS-induced expression of catabolic factors, the release of IL-1β, as well as the nuclear translocation of NF-κB and β-catenin. TNKS-1/2 expression increased in mild and moderate OA cartilage. Our results demonstrated that XAV939 suppressed mechanical stress-induced expression of catabolic proteases by the inhibition of NF-κB and activation of β-catenin, indicating that TNKS-1/2 expression might be associated with OA pathogenesis. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Cartilage Biology and Applications in Regenerative Medicine)

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16 pages, 7281 KiB

Open AccessArticle

WGA-M001, a Mixture of Total Extracts of Tagetes erecta and Ocimum basilicum, Synergistically Alleviates Cartilage Destruction by Inhibiting ERK and NF-κB Signaling

by Eunjeong Oh, Hahyeong Jang, Subin Ok, Jiwon Eom, Hyunyong Lee, Sung Hun Kim, Jong Hwa Kim, Yu Mi Jeong, Kyeong Jin Kim, Seung Pil Yun, Hyung-Jun Kwon, In-Chul Lee, Ji-Young Park and Siyoung Yang

Int. J. Mol. Sci. 2023, 24(24), 17459; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms242417459 - 14 Dec 2023

Viewed by 899

Abstract

Tagetes erecta and Ocimum basilicum are medicinal plants that exhibit anti-inflammatory effects against various diseases. However, their individual and combined effects on osteoarthritis (OA) are unknown. Herein, we aimed to demonstrate the effects of T. erecta, O. basilicum, and their mixture, WGA-M001, on OA pathogenesis. The administration of total extracts of T. erecta and O. basilicum reduced cartilage degradation and inflammation without causing cytotoxicity. Although WGA-M001 contained lower concentrations of the individual extracts, it strongly inhibited the expression of pathogenic factors. In vivo OA studies also supported that WGA-M001 had protective effects against cartilage destruction at lower doses than those of T. erecta and O. basilicum. Moreover, its effects were stronger than those observed using Boswellia and Perna canaliculus. WGA-M001 effectively inhibited the interleukin (IL)-1β-induced nuclear factor kappa-light-chain-enhancer of the activated B cell (NF-κB) pathway and ERK phosphorylation. Furthermore, RNA-sequence analysis also showed that WGA-M001 decreased the expression of genes related to the IL-1β-induced NF-κB and ERK signaling pathways. Therefore, WGA-M001 is more effective than the single total extracts of T. erecta and O. basilicum in attenuating OA progression by regulating ERK and NF-κB signaling. Our results open new possibilities for WGA-M001 as a potential therapeutic agent for OA treatment. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Cartilage Biology and Applications in Regenerative Medicine)

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20 pages, 12918 KiB

Open AccessArticle

Rheumatoid Synovial Fluid and Acidic Extracellular pH Modulate the Immunomodulatory Activity of Urine-Derived Stem Cells

by Michaela Cehakova, Dana Ivanisova, Magdalena Strecanska, Jana Plava, Zuzana Varchulova Novakova, Andreas Nicodemou, Stefan Harsanyi, Martina Culenova, Sona Bernatova and Lubos Danisovic

Int. J. Mol. Sci. 2023, 24(21), 15856; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms242115856 - 1 Nov 2023

Cited by 1 | Viewed by 909

Abstract

Urine-derived stem cells (UdSCs) possess a remarkable anti-inflammatory and immune-modulating activity. However, the clinical significance of UdSCs in autoimmune inflammatory diseases such as rheumatoid arthritis (RA) is yet to be explored. Hence, we tested the UdSCs response to an articular RA microenvironment. To simulate the inflamed RA joint more authentically in vitro, we treated cells with rheumatoid synovial fluids (RASFs) collected from RA patients, serum deprivation, acidosis (pH 7.0 and 6.5), and their combinations. Firstly, the RASFs pro-inflammatory status was assessed by cytokine quantification. Then, UdSCs were exposed to the RA environmental factors for 48 h and cell proliferation, gene expression and secretion of immunomodulatory factors were evaluated. The immunosuppressive potential of pre-conditioned UdSCs was also assessed via co-cultivation with activated peripheral blood mononuclear cells (PBMCs). In all experimental conditions, UdSCs’ proliferation was not affected. Conversely, extracellular acidosis considerably impaired the viability/proliferation of adipose tissue-derived stem cells (ATSCs). In the majority of cases, exposure to RA components led to the upregulated expression of IL-6, TSG6, ICAM-1, VCAM-1, and PD-L1, all involved in immunomodulation. Upon RASFs and acidic stimulation, UdSCs secreted higher levels of immunomodulatory cytokines: IL-6, IL-8, MCP-1, RANTES, GM-CSF, and IL-4. Furthermore, RASFs and combined pretreatment with RASFs and acidosis promoted the UdSCs-mediated immunosuppression and the proliferation of activated PBMCs was significantly inhibited. Altogether, our data indicate that the RA microenvironment certainly has the capacity to enhance UdSCs’ immunomodulatory function. For potential preclinical/clinical applications, the intra-articular injection might be a reasonable approach to maximize UdSCs’ therapeutic efficiency in the RA treatment. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Cartilage Biology and Applications in Regenerative Medicine)

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Review

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25 pages, 2108 KiB

Open AccessReview

Human Chondrocytes, Metabolism of Articular Cartilage, and Strategies for Application to Tissue Engineering

by Darina Bačenková, Marianna Trebuňová, Jana Demeterová and Jozef Živčák

Int. J. Mol. Sci. 2023, 24(23), 17096; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms242317096 - 4 Dec 2023

Cited by 2 | Viewed by 1855

Abstract

Hyaline cartilage, which is characterized by the absence of vascularization and innervation, has minimal self-repair potential in case of damage and defect formation in the chondral layer. Chondrocytes are specialized cells that ensure the synthesis of extracellular matrix components, namely type II collagen and aggregen. On their surface, they express integrins CD44, α1β1, α3β1, α5β1, α10β1, αVβ1, αVβ3, and αVβ5, which are also collagen-binding components of the extracellular matrix. This article aims to contribute to solving the problem of the possible repair of chondral defects through unique methods of tissue engineering, as well as the process of pathological events in articular cartilage. In vitro cell culture models used for hyaline cartilage repair could bring about advanced possibilities. Currently, there are several variants of the combination of natural and synthetic polymers and chondrocytes. In a three-dimensional environment, chondrocytes retain their production capacity. In the case of mesenchymal stromal cells, their favorable ability is to differentiate into a chondrogenic lineage in a three-dimensional culture. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Cartilage Biology and Applications in Regenerative Medicine)

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30 pages, 6039 KiB

Open AccessReview

The Role of Genetics and Epigenetic Regulation in the Pathogenesis of Osteoarthritis

by Kajetan Kiełbowski, Mariola Herian, Estera Bakinowska, Bolesław Banach, Tomasz Sroczyński and Andrzej Pawlik

Int. J. Mol. Sci. 2023, 24(14), 11655; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241411655 - 19 Jul 2023

Cited by 6 | Viewed by 2594

Abstract

Osteoarthritis (OA) is progressive disease characterised by cartilage degradation, subchondral bone remodelling and inflammation of the synovium. The disease is associated with obesity, mechanical load and age. However, multiple pro-inflammatory immune mediators regulate the expression of metalloproteinases, which take part in cartilage degradation. Furthermore, genetic factors also contribute to OA susceptibility. Recent studies have highlighted that epigenetic mechanisms may regulate the expression of OA-associated genes. This review aims to present the mechanisms of OA pathogenesis and summarise current evidence regarding the role of genetics and epigenetics in this process. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Cartilage Biology and Applications in Regenerative Medicine)

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