Biology of Osteoarthritis

A special issue of Biology (ISSN 2079-7737).

Deadline for manuscript submissions: closed (30 November 2020) | Viewed by 44774

Special Issue Editors

Special Issue Information

Dear Colleagues,

Osteoarthritis is a severe, chronic joint disorder affecting millions of people worldwide, for which there is no reliable cure to date. The degradation of the articular cartilage is a central feature of the disease, but osteoarthritis is also associated with pathological changes in all other joint tissues, including a remodelling of the subchondral bone; inflammation of the synovium; and injuries in the meniscus, tendons, and ligaments. As none of the current therapeutic options can prevent the progression of the disease or restore damaged joint tissues in their structures and functions, there is an urgent need to better understand the pathomechanisms underlying osteoarthritic changes in patients. The goal of this Special Issue is to offer an overview of the most advanced knowledge on osteoarthritis that may allow one to develop novel regimens against this serious, global disorder.

Prof. Dr. Magali Cucchiarini
Prof. Dr. Henning Madry
Guest Editors

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Keywords

  • metabolism
  • inflammation
  • aging
  • biomechanics
  • gene regulation
  • crosstalks
  • development
  • imaging
  • biomarkers
  • disease modeling

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Published Papers (5 papers)

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Research

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20 pages, 2725 KiB  
Article
Impact of Isolation Procedures on the Development of a Preclinical Synovial Fibroblasts/Macrophages in an In Vitro Model of Osteoarthritis
by Cristina Manferdini, Yasmin Saleh, Paolo Dolzani, Elena Gabusi, Diego Trucco, Giuseppe Filardo and Gina Lisignoli
Biology 2020, 9(12), 459; https://doi.org/10.3390/biology9120459 - 10 Dec 2020
Cited by 6 | Viewed by 4021
Abstract
There is a lack ofin vitromodels able to properly represent osteoarthritis (OA) synovial tissue (ST). We aimed to characterize OA ST and to investigate whether a mechanical or enzymatic digestion procedures influence synovial cell functional heterogeneity in vitro. Procedures using mechanical nondigested fragments [...] Read more.
There is a lack ofin vitromodels able to properly represent osteoarthritis (OA) synovial tissue (ST). We aimed to characterize OA ST and to investigate whether a mechanical or enzymatic digestion procedures influence synovial cell functional heterogeneity in vitro. Procedures using mechanical nondigested fragments (NDF), synovial digested fragments (SDF), and filtrated synovial digested cells (SDC) were compared. An immunophenotypic profile was performed to distinguish synovial fibroblasts (CD55, CD73, CD90, CD106), macrophages (CD14, CD68), M1-like (CD80, CD86), and M2-like (CD163, CD206) synovial macrophages. Pro-inflammatory (interleukin 6 IL6), tumor necrosis factor alpha (TNFα), chemokine C-C motif ligand 3 (CCL3/MIP1α), C-X- motif chemokine ligand 10 (CXCL10/IP10) and anti-inflammatory (interleukin 10 (IL10)), transforming growth factor beta 1 (TGFβ1), C-C motif chemokine ligand 18 (CCL18) cytokines were evaluated. CD68 and CD163 markers were higher in NDF and SDF compared to the SDC procedure, while CD80, CD86, and CD206 were higher only in NDF compared to the SDC procedure. Synovial fibroblast markers showed similar percentages. TNFα, CCL3/MIP1α, CXCL10/IP10, and CCL18 were higher in NDF compared to SDC, but not compared to SDF. IL10 and TGFβ1 were higher in NDF than SDC at the molecular level, while IL6 did not show differences among procedures. We demonstrated that NDF isolation procedures better preserved the heterogeneity of specific OA synovial populations (fibroblasts, macrophages), fostering their use for testing new cell therapies or drugs for OA, reducing or avoiding the use of animal models. Full article
(This article belongs to the Special Issue Biology of Osteoarthritis)
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21 pages, 8238 KiB  
Article
Physioxia Expanded Bone Marrow Derived Mesenchymal Stem Cells Have Improved Cartilage Repair in an Early Osteoarthritic Focal Defect Model
by Girish Pattappa, Jonas Krueckel, Ruth Schewior, Dustin Franke, Alexander Mench, Matthias Koch, Johannes Weber, Siegmund Lang, Christian G. Pfeifer, Brian Johnstone, Denitsa Docheva, Volker Alt, Peter Angele and Johannes Zellner
Biology 2020, 9(8), 230; https://doi.org/10.3390/biology9080230 - 17 Aug 2020
Cited by 18 | Viewed by 3604
Abstract
Focal early osteoarthritis (OA) or degenerative lesions account for 60% of treated cartilage defects each year. The current cell-based regenerative treatments have an increased failure rate for treating degenerative lesions compared to traumatic defects. Mesenchymal stem cells (MSCs) are an alternative cell source [...] Read more.
Focal early osteoarthritis (OA) or degenerative lesions account for 60% of treated cartilage defects each year. The current cell-based regenerative treatments have an increased failure rate for treating degenerative lesions compared to traumatic defects. Mesenchymal stem cells (MSCs) are an alternative cell source for treating early OA defects, due to their greater chondrogenic potential, compared to early OA chondrocytes. Low oxygen tension or physioxia has been shown to enhance MSC chondrogenic matrix content and could improve functional outcomes of regenerative therapies. The present investigation sought to develop a focal early OA animal model to evaluate cartilage regeneration and hypothesized that physioxic MSCs improve in vivo cartilage repair in both, post-trauma and focal early OA defects. Using a rabbit model, a focal defect was created, that developed signs of focal early OA after six weeks. MSCs cultured under physioxia had significantly enhanced in vitro MSC chondrogenic GAG content under hyperoxia with or without the presence of interleukin-1β (IL-1β). In both post-traumatic and focal early OA defect models, physioxic MSC treatment demonstrated a significant improvement in cartilage repair score, compared to hyperoxic MSCs and respective control defects. Future investigations will seek to understand whether these results are replicated in large animal models and the underlying mechanisms involved in in vivo cartilage regeneration. Full article
(This article belongs to the Special Issue Biology of Osteoarthritis)
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18 pages, 2357 KiB  
Review
Over-Production of Therapeutic Growth Factors for Articular Cartilage Regeneration by Protein Production Platforms and Protein Packaging Cell Lines
by Ali Mobasheri, Heonsik Choi and Pablo Martín-Vasallo
Biology 2020, 9(10), 330; https://doi.org/10.3390/biology9100330 - 9 Oct 2020
Cited by 5 | Viewed by 4739
Abstract
This review article focuses on the current state-of-the-art cellular and molecular biotechnology for the over-production of clinically relevant therapeutic and anabolic growth factors. We discuss how the currently available tools and emerging technologies can be used for the regenerative treatment of osteoarthritis (OA). [...] Read more.
This review article focuses on the current state-of-the-art cellular and molecular biotechnology for the over-production of clinically relevant therapeutic and anabolic growth factors. We discuss how the currently available tools and emerging technologies can be used for the regenerative treatment of osteoarthritis (OA). Transfected protein packaging cell lines such as GP-293 cells may be used as “cellular factories” for large-scale production of therapeutic proteins and pro-anabolic growth factors, particularly in the context of cartilage regeneration. However, when irradiated with gamma or x-rays, these cells lose their capacity for replication, which makes them safe for use as a live cell component of intra-articular injections. This innovation is already here, in the form of TissueGene-C, a new biological drug that consists of normal allogeneic primary chondrocytes combined with transduced GP2-293 cells that overexpress the growth factor transforming growth factor β1 (TGF-β1). TissueGene-C has revolutionized the concept of cell therapy, allowing drug companies to develop live cells as biological drug delivery systems for direct intra-articular injection of growth factors whose half-lives are in the order of minutes. Therefore, in this paper, we discuss the potential for new innovations in regenerative medicine for degenerative diseases of synovial joints using mammalian protein production platforms, specifically protein packaging cell lines, for over-producing growth factors for cartilage tissue regeneration and give recent examples. Mammalian protein production platforms that incorporate protein packaging eukaryotic cell lines are superior to prokaryotic bacterial expression systems and are likely to have a significant impact on the development of new humanized biological growth factor therapies for treating focal cartilage defects and more generally for the treatment of degenerative joint diseases such as OA, especially when injected directly into the joint. Full article
(This article belongs to the Special Issue Biology of Osteoarthritis)
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31 pages, 4731 KiB  
Review
Transcription Factors in Cartilage Homeostasis and Osteoarthritis
by Margot Neefjes, Arjan P. M. van Caam and Peter M. van der Kraan
Biology 2020, 9(9), 290; https://doi.org/10.3390/biology9090290 - 14 Sep 2020
Cited by 21 | Viewed by 6106
Abstract
Osteoarthritis (OA) is the most common degenerative joint disease, and it is characterized by articular cartilage loss. In part, OA is caused by aberrant anabolic and catabolic activities of the chondrocyte, the only cell type present in cartilage. These chondrocyte activities depend on [...] Read more.
Osteoarthritis (OA) is the most common degenerative joint disease, and it is characterized by articular cartilage loss. In part, OA is caused by aberrant anabolic and catabolic activities of the chondrocyte, the only cell type present in cartilage. These chondrocyte activities depend on the intra- and extracellular signals that the cell receives and integrates into gene expression. The key proteins for this integration are transcription factors. A large number of transcription factors exist, and a better understanding of the transcription factors activated by the various signaling pathways active during OA can help us to better understand the complex etiology of OA. In addition, establishing such a profile can help to stratify patients in different subtypes, which can be a very useful approach towards personalized therapy. In this review, we discuss crucial transcription factors for extracellular matrix metabolism, chondrocyte hypertrophy, chondrocyte senescence, and autophagy in chondrocytes. In addition, we discuss how insight into these factors can be used for treatment purposes. Full article
(This article belongs to the Special Issue Biology of Osteoarthritis)
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32 pages, 1754 KiB  
Review
Pathogenesis of Osteoarthritis: Risk Factors, Regulatory Pathways in Chondrocytes, and Experimental Models
by Yuchen He, Zhong Li, Peter G. Alexander, Brian D. Ocasio-Nieves, Lauren Yocum, Hang Lin and Rocky S. Tuan
Biology 2020, 9(8), 194; https://doi.org/10.3390/biology9080194 - 29 Jul 2020
Cited by 172 | Viewed by 25229
Abstract
As the most common chronic degenerative joint disease, osteoarthritis (OA) is the leading cause of pain and physical disability, affecting millions of people worldwide. Mainly characterized by articular cartilage degradation, osteophyte formation, subchondral bone remodeling, and synovial inflammation, OA is a heterogeneous disease [...] Read more.
As the most common chronic degenerative joint disease, osteoarthritis (OA) is the leading cause of pain and physical disability, affecting millions of people worldwide. Mainly characterized by articular cartilage degradation, osteophyte formation, subchondral bone remodeling, and synovial inflammation, OA is a heterogeneous disease that impacts all component tissues of the articular joint organ. Pathological changes, and thus symptoms, vary from person to person, underscoring the critical need of personalized therapies. However, there has only been limited progress towards the prevention and treatment of OA, and there are no approved effective disease-modifying osteoarthritis drugs (DMOADs). Conventional treatments, including non-steroidal anti-inflammatory drugs (NSAIDs) and physical therapy, are still the major remedies to manage the symptoms until the need for total joint replacement. In this review, we provide an update of the known OA risk factors and relevant mechanisms of action. In addition, given that the lack of biologically relevant models to recapitulate human OA pathogenesis represents one of the major roadblocks in developing DMOADs, we discuss current in vivo and in vitro experimental OA models, with special emphasis on recent development and application potential of human cell-derived microphysiological tissue chip platforms. Full article
(This article belongs to the Special Issue Biology of Osteoarthritis)
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