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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (15 November 2023) | Viewed by 33211

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Dr. Laura Mangiavini

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Department of Biomedical Sciences for Health, University of Milan, 20133 Milan, Italy
Interests: articular cartilage; cartilage lesions; tissue engineering; cell therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Articular cartilage is a complex tissue; once damaged, it is not able to regenerate. Hence, articular cartilage repair is still challenging for orthopaedic surgeons. The successful treatment of cartilage lesions is fundamental to avoid the onset of degenerative processes often leading to osteoarthritis. In the earliest stage of cartilage lesions, cell therapy combined with tissue engineering strategies can be effective to promote tissue regeneration and counteract the chronicization of catabolic processes.

This Special Issue welcomes original papers and reviews focused on novel cell therapies or tissue engineering strategies for cartilage regeneration. We accept original manuscripts aimed at basic research and the treatment of both acute and chronic cartilage lesions.

Dr. Laura Mangiavini
Guest Editor

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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.

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Keywords

articular cartilage
cartilage lesions
tissue engineering
cell therapy

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Advances in Molecular Research of Cartilage: 2nd Edition in International Journal of Molecular Sciences

Published Papers (9 papers)

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Research

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19 pages, 10222 KiB

Open AccessArticle

Does Chronic Pancreatitis in Growing Pigs Lead to Articular Cartilage Degradation and Alterations in Subchondral Bone?

by Ewa Tomaszewska, Monika Hułas-Stasiak, Piotr Dobrowolski, Małgorzata Świątkiewicz, Siemowit Muszyński, Agnieszka Tomczyk-Warunek, Tomasz Blicharski, Janine Donaldson, Marcin B. Arciszewski, Michał Świetlicki, Iwona Puzio and Joanna Bonior

Int. J. Mol. Sci. 2024, 25(4), 1989; https://doi.org/10.3390/ijms25041989 - 6 Feb 2024

Cited by 3 | Viewed by 1533

Abstract

Chronic pancreatitis (CP), a progressive inflammatory disease, poses diagnostic challenges due to its initially asymptomatic nature. While CP’s impact on exocrine and endocrine functions is well-recognized, its potential influence on other body systems, particularly in young individuals, remains underexplored. This study investigates the hypothesis that CP in growing pigs leads to alterations in articular cartilage and subchondral bone, potentially contributing to osteoarthritis (OA) development. Utilizing a pig model of cerulein-induced CP, we examined the structural and compositional changes in subchondral bone, articular cartilage, and synovial fluid. Histological analyses, including Picrosirius Red and Safranin-O staining, were employed alongside immuno-histochemistry and Western blotting techniques. Our findings reveal significant changes in the subchondral bone, including reduced bone volume and alterations in collagen fiber composition. Articular cartilage in CP pigs exhibited decreased proteoglycan content and alterations in key proteins such as MMP-13 and TGF-β1, indicative of early cartilage degradation. These changes suggest a link between CP and musculoskeletal alterations, underscoring the need for further research into CP’s systemic effects. Our study provides foundational insights into the relationship between CP and skeletal health, potentially guiding future pediatric healthcare strategies for early CP diagnosis and management. Full article

(This article belongs to the Special Issue Advances in Molecular Research of Cartilage)

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16 pages, 2325 KiB

Open AccessArticle

Mesenchymal Stem Cells Cultured in a 3D Microgel Environment Containing Platelet-Rich Plasma Significantly Modify Their Chondrogenesis-Related miRNA Expression

by Manuel Mata, Rubén Salvador-Clavell, Joaquín Ródenas-Rochina, María Sancho-Tello, Gloria Gallego Ferrer and José Luis Gómez Ribelles

Int. J. Mol. Sci. 2024, 25(2), 937; https://doi.org/10.3390/ijms25020937 - 11 Jan 2024

Cited by 2 | Viewed by 1207

Abstract

The aim of this work is to study the effect of platelet factors on the differentiation of mesenchymal stem cells (MSCs) to hyaline cartilage chondrocytes in a three-dimensional environment. MSCs were cultured in a microgel environment with a chondrogenic medium. The microgel consisted of microspheres that combine gelatin and platelet-rich plasma (PRP). The gelatin/PRP microdroplets were produced by emulsion. The gelatin containing the microdroplets was enzymatically gelled, retaining PRP and, just before seeding the cells, platelets were activated by adding calcium chloride so that platelet growth factors were released into the culture media but not before. Platelet activation was analyzed before activation to rule out the possibility that the gelatin cross-linking process itself activated the platelets. The gene expression of characteristic chondrogenic markers and miRNA expression were analyzed in cells cultured in a differentiation medium and significant differences were found between gelation/PRP microgels and those containing only pure gelatin. In summary, the gelatin microspheres effectively encapsulated platelets that secreted and released factors that significantly contributed to cellular chondrogenic differentiation. At the same time, the microgel constituted a 3D medium that provided the cells with adherent surfaces and the possibility of three-dimensional cell–cell contact. Full article

(This article belongs to the Special Issue Advances in Molecular Research of Cartilage)

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17 pages, 7828 KiB

Open AccessArticle

PSD95 as a New Potential Therapeutic Target of Osteoarthritis: A Study of the Identification of Hub Genes through Self-Contrast Model

by Ping Huang, Jieming Lin, Hongxing Shen and Xiang Zhao

Int. J. Mol. Sci. 2023, 24(19), 14682; https://doi.org/10.3390/ijms241914682 - 28 Sep 2023

Cited by 1 | Viewed by 1415

Abstract

Osteoarthritis (OA) is a worldwide joint disease. However, the precise mechanism causing OA remains unclear. Our primary aim was to identify vital biomarkers associated with the mechano-inflammatory aspect of OA, providing potential diagnostic and therapeutic targets for OA. Thirty OA patients who underwent total knee arthroplasty were recruited, and cartilage samples were obtained from both the lateral tibial plateau (LTP) and medial tibial plateau (MTP). GO and KEGG enrichment analyses were performed, and the protein–protein interaction (PPI) assessment was conducted for hub genes. The effect of PSD95 inhibition on cartilage degeneration was also conducted and analyzed. A total of 1247 upregulated and 244 downregulated DEGs were identified. Significant differences were observed between MTP and LTP in mechanical stress-related genes and activated sensory neurons based on a self-contrast model of human knee OA. Cluster analysis identified DLG4 as the hub gene. Cyclic loading stress increased PSD95 (encoded by DLG4) expression in LTP cartilage, and PSD95 inhibitors could alleviate OA progression. This study suggests that inhibiting PSD95 could be a potential therapeutic strategy for preventing articular cartilage degradation. Full article

(This article belongs to the Special Issue Advances in Molecular Research of Cartilage)

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14 pages, 3272 KiB

Open AccessArticle

Expression Profiles of Long Non-Coding RNAs in the Articular Cartilage of Rats Exposed to T-2 Toxin

by Fangfang Yu, Miao Wang, Kangting Luo, Lei Sun, Shuiyuan Yu, Juan Zuo and Yanjie Wang

Int. J. Mol. Sci. 2023, 24(18), 13703; https://doi.org/10.3390/ijms241813703 - 5 Sep 2023

Cited by 1 | Viewed by 1105

Abstract

T-2 toxin could induce bone damage. But there is no specific mechanism about the long non-coding RNAs (lncRNAs) involved in T-2 toxin-induced articular cartilage injury. In this study, 24 SD rats were randomly divided into a control group and a T-2 group, which were administered 4% absolute ethanol and 100 ng/g · bw/day of T-2 toxin, respectively. After treatment for 4 weeks, safranin O/fast green staining identified the pathological changes in the articular cartilage of rats, and immunofluorescence verified the autophagy level increase in the T-2 group. Total RNA was isolated, and high-throughput sequencing was performed. A total of 620 differentially expressed lncRNAs (DE-lncRNAs) were identified, and 326 target genes were predicted. Enrichment analyses showed that the target genes of DE-lncRNAs were enriched in the autophagy-related biological processes and pathways. According to the autophagy database, a total of 23 autophagy-related genes were identified, and five hub genes (Foxo3, Foxo1, Stk11, Hdac4, and Rela) were screened using the Maximal Clique Centrality algorithm. The Human Protein Atlas database indicated that Rela and Hdac4 proteins were highly expressed in the bone marrow tissue, while Foxo3, Foxo1, and Stk11 proteins were reduced. According to Enrichr, etoposide and diatrizoic acid were identified as the key drugs. The real-time quantitative PCR results were consistent with the RNA sequencing (RNA-Seq) results. These results suggested that autophagy was involved in the rat articular cartilage lesions induced by T-2 toxin. The lncRNAs of NONRATG014223.2, NONRATG012484.2, NONRATG021591.2, NONRATG024691.2, and NONRATG002808.2, and their target genes of Foxo3, Foxo1, Stk11, Hdac4, and Rela, respectively, were the key regulator factors of autophagy. Full article

(This article belongs to the Special Issue Advances in Molecular Research of Cartilage)

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17 pages, 5229 KiB

Open AccessArticle

In Vitro and In Vivo Biocompatibility Assessment of a Thermosensitive Injectable Chitosan-Based Hydrogel for Musculoskeletal Tissue Engineering

by Barbara Canciani, Francesca Semeraro, Valentina Rafaela Herrera Millar, Francesca Gervaso, Alessandro Polini, Antonella Stanzione, Giuseppe Michele Peretti, Alessia Di Giancamillo and Laura Mangiavini

Int. J. Mol. Sci. 2023, 24(13), 10446; https://doi.org/10.3390/ijms241310446 - 21 Jun 2023

Cited by 6 | Viewed by 2004

Abstract

Musculoskeletal impairments, especially cartilage and meniscus lesions, are some of the major contributors to disabilities. Thus, novel tissue engineering strategies are being developed to overcome these issues. In this study, the aim was to investigate the biocompatibility, in vitro and in vivo, of a thermosensitive, injectable chitosan-based hydrogel loaded with three different primary mesenchymal stromal cells. The cell types were human adipose-derived mesenchymal stromal cells (hASCs), human bone marrow stem cells (hBMSCs), and neonatal porcine infrapatellar fat-derived cells (IFPCs). For the in vitro study, the cells were encapsulated in sol-phase hydrogel, and then, analyzed via live/dead assay at 1, 4, 7, and 14 days to compare their capacity to survive in the hydrogel. To assess biocompatibility in vivo, cellularized scaffolds were subcutaneously implanted in the dorsal pouches of nude mice and analyzed at 4 and 12 weeks. Our data showed that all the different cell types survived (the live cell percentages were between 60 and 80 at all time points in vitro) and proliferated in the hydrogel (from very few at 4 weeks to up to 30% at 12 weeks in vivo); moreover, the cell-laden hydrogels did not trigger an immune response in vivo. Hence, our hydrogel formulation showed a favorable profile in terms of safety and biocompatibility, and it may be applied in tissue engineering strategies for cartilage and meniscus repair. Full article

(This article belongs to the Special Issue Advances in Molecular Research of Cartilage)

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13 pages, 4370 KiB

Open AccessArticle

Irisin Modulates Inflammatory, Angiogenic, and Osteogenic Factors during Fracture Healing

by Angela Oranger, Roberta Zerlotin, Cinzia Buccoliero, Lorenzo Sanesi, Giuseppina Storlino, Ernestina Schipani, Kenneth Michael Kozloff, Giorgio Mori, Graziana Colaianni, Silvia Colucci and Maria Grano

Int. J. Mol. Sci. 2023, 24(3), 1809; https://doi.org/10.3390/ijms24031809 - 17 Jan 2023

Cited by 14 | Viewed by 2730

Abstract

Bone fractures are a widespread clinical event due to accidental falls and trauma or bone fragility; they also occur in association with various diseases and are common with aging. In the search for new therapeutic strategies, a crucial link between irisin and bone fractures has recently emerged. To explore this issue, we subjected 8-week-old C57BL/6 male mice to tibial fracture, and then we treated them with intra-peritoneal injection of r-Irisin (100 µg/kg/weekly) or vehicle as control. At day 10 post fracture, histological analysis showed a significant reduced expression of inflammatory cytokines as tumor necrosis factor-alpha (TNFα) (p = 0.004) and macrophage inflammatory protein-alpha (MIP-1α) (p = 0.015) in the cartilaginous callus of irisin-treated mice compared to controls, supporting irisin’s anti-inflammatory role. We also found increased expressions of the pro-angiogenic molecule vascular endothelial growth factor (VEGF) (p = 0.002) and the metalloproteinase MMP-13 (p = 0.0006) in the irisin-treated mice compared to the vehicle ones, suggesting a myokine involvement in angiogenesis and cartilage matrix degradation processes. Moreover, the bone morphogenetic protein (BMP2) expression was also upregulated (p = 0.002). Taken together, our findings suggest that irisin can contribute to fracture repair by reducing inflammation and promoting vessel invasion, matrix degradation, and bone formation, supporting its possible role as a novel molecule for fracture treatment. Full article

(This article belongs to the Special Issue Advances in Molecular Research of Cartilage)

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Review

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13 pages, 644 KiB

Open AccessReview

Targeting Adenosine Signalling in Knee Chondropathy: The Combined Action of Polydeoxyribonucleotide and Pulsed Electromagnetic Fields: A Current Concept Review

by Lorenzo Moretti, Davide Bizzoca, Alessandro Geronimo, Andrea Michele Abbaticchio, Francesco Luca Moretti, Arianna Carlet, Francesco Fischetti and Biagio Moretti

Int. J. Mol. Sci. 2023, 24(12), 10090; https://doi.org/10.3390/ijms241210090 - 13 Jun 2023

Cited by 2 | Viewed by 2088

Abstract

Chondropathy of the knee is one of the most frequent degenerative cartilage pathologies with advancing age. Scientific research has, in recent years, advanced new therapies that target adenosine A2 receptors, which play a significant role in human health against many disease states by activating different protective effects against cell sufferance and damage. Among these, it has been observed that intra-articular injections of polydeoxyribonucleotides (PDRN) and Pulsed Electromagnetic Fields (PEMF) can stimulate the adenosine signal, with significant regenerative and healing effects. This review aims to depict the role and therapeutic modulation of A2A receptors in knee chondropathy. Sixty articles aimed at providing data for our study were included in this review. The present paper highlights how intra-articular injections of PDRN create beneficial effects by reducing pain and improving functional clinical scores, thanks to their anti-inflammatory action and the important healing and regenerating power of the stimulation of cell growth, production of collagen, and the extracellular matrix. PEMF therapy is a valid option in the conservative treatment of different articular pathologies, including early OA, patellofemoral pain syndrome, spontaneous osteonecrosis of the knee (SONK), and in athletes. PEMF could also be used as a supporting therapy after an arthroscopic knee procedure total knee arthroplasty to reduce the post-operative inflammatory state. The proposal of new therapeutic approaches capable of targeting the adenosine signal, such as the intra-articular injection of PDRN and the use of PEMF, has shown excellent beneficial results compared to conventional treatments. These are presented as an extra weapon in the fight against knee chondropathy. Full article

(This article belongs to the Special Issue Advances in Molecular Research of Cartilage)

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22 pages, 1019 KiB

Open AccessReview

RNA Extraction from Cartilage: Issues, Methods, Tips

by Stefania Pagani, Melania Maglio, Laura Sicuro, Milena Fini, Gianluca Giavaresi and Silvia Brogini

Int. J. Mol. Sci. 2023, 24(3), 2120; https://doi.org/10.3390/ijms24032120 - 20 Jan 2023

Cited by 2 | Viewed by 4154

Abstract

The increase in degenerative diseases involving articular cartilage has pushed research to focus on their pathogenesis and treatment, exploiting increasingly complex techniques. Gene expression analyses from tissue are representative of the in vivo situation, but the protocols to be applied to obtain a reliable analysis are not completely cleared through customs. Thus, RNA extraction from fresh samples and specifically from musculoskeletal tissue such as cartilage is still a challenging issue. The aim of the review is to provide an overview of the techniques described in the literature for RNA extraction, highlighting limits and possibilities. The research retrieved 65 papers suitable for the purposes. The results highlighted the great difficulty in comparing the different studies, both for the sources of tissue used and for the techniques employed, as well as the details about protocols. Few papers compared different RNA extraction methods or homogenization techniques; the case study reported by authors about RNA extraction from sheep cartilage has not found an analog in the literature, confirming the existence of a relevant blank on studies about RNA extraction from cartilage tissue. However, the state of the art depicted can be used as a starting point to improve and expand studies on this topic. Full article

(This article belongs to the Special Issue Advances in Molecular Research of Cartilage)

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16 pages, 2165 KiB

Open AccessReview

Discogenic Low Back Pain: Anatomy, Pathophysiology and Treatments of Intervertebral Disc Degeneration

by Isma Liza Mohd Isa, Seong Lin Teoh, Nurul Huda Mohd Nor and Sabarul Afian Mokhtar

Int. J. Mol. Sci. 2023, 24(1), 208; https://doi.org/10.3390/ijms24010208 - 22 Dec 2022

Cited by 90 | Viewed by 15718

Abstract

Intervertebral disc (IVD) degeneration is a major contributing factor for discogenic low back pain (LBP), causing a significant global disability. The IVD consists of an inner core proteoglycan-rich nucleus pulposus (NP) and outer lamellae collagen-rich annulus fibrosus (AF) and is confined by a cartilage end plate (CEP), providing structural support and shock absorption against mechanical loads. Changes to degenerative cascades in the IVD cause dysfunction and instability in the lumbar spine. Various treatments include pharmacological, rehabilitation or surgical interventions that aim to relieve pain; however, these modalities do not halt the pathologic events of disc degeneration or promote tissue regeneration. Loss of stem and progenitor markers, imbalance of the extracellular matrix (ECM), increase of inflammation, sensory hyperinnervation and vascularization, and associated signaling pathways have been identified as the onset and progression of disc degeneration. To better understand the pain originating from IVD, our review focuses on the anatomy of IVD and the pathophysiology of disc degeneration that contribute to the development of discogenic pain. We highlight the key mechanisms and associated signaling pathways underlying disc degeneration causing discogenic back pain, current clinical treatments, clinical perspective and directions of future therapies. Our review comprehensively provides a better understanding of healthy IVD and degenerative events of the IVD associated with discogenic pain, which helps to model painful disc degeneration as a therapeutic platform and to identify signaling pathways as therapeutic targets for the future treatment of discogenic pain. Full article

(This article belongs to the Special Issue Advances in Molecular Research of Cartilage)

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