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Cell and Molecular Causes of Joint Inflammation and Damage

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A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Motility and Adhesion".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 29265

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Special Issue Editor

Prof. Dr. Gundula Schulze-Tanzil

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Guest Editor

Institute of Anatomy and Cell Biology, Paracelsus Medical University, Nuremberg, Germany
Interests: extracellular matrix (ECM); tissue engineering; glycosaminoglycans; tendons; joint inflammation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Osteoarthritis (OA) leads to irreversible joint damage and progressive loss of function. Being also associated with aging it gets increasing importance in the aging population worldwide. Hence, OA remains a large challenge since so far no effective therapeutic options are available. On the molecular level the osteoarthritic articular cartilage shows cartilage extracellular matrix degradation, chondrocytes apoptosis, catabolic response and mitochondrial stress. In addition to cartilage many other joint associated tissues are affected by OA reflecting features such as synovitis, bone sclerosis, bone edema and ligament degeneration. Since its molecular pathogenesis is still poorly understood much more research has to be undertaken to establish a solid basis for future therapeutic interventions.

Therefore, this special issue aims to summarize emerging novel insights into the molecular pathogenesis of OA with a strong focus on the interrelation between inflammatory and chondroprotective signalling pathways as well as dysbalances of the joint-related immune responses. It should also address the contribution of systemic metabolic disorders such as diabetes mellitus to OA leading to its accelerated pathogenesis. The interplay and involvement of all cell types and tissues in the joint as well as precursor cells in the scenario of osteoarthritic joint damage will be addressed to get a more global picture of OA pathogenesis and its mode of progression. Mechanisms of direct and indirect cell-cell communication e.g. by the exchange of soluble mediators, such as cytokines, chemokines, miRNAs, the role of exosomes containing these factors facilitating cell responses and direct receptor-mediated cell-cell interactions will be accounted.

We hope that the expected insight into its molecular pathogenesis will provide a novel understanding of OA as the worldwide most important joint disease.

We are looking forward to your contributions to this Special Issue.

Prof. Dr. Gundula Schulze-Tanzil
Guest Editor

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Keywords

osteoarthritis
joint inflammation
cartilage degradation
complement activation
exosomes
hyperglycemia
diabetes mellitus
synovitis
proinflammatory cytokines

Published Papers (5 papers)

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Research

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16 pages, 2783 KiB

Open AccessArticle

Infrapatellar Fat Pad Modulates Osteoarthritis-Associated Cytokine and MMP Expression in Human Articular Chondrocytes

by Ewa Wisniewska, Dominik Laue, Jacob Spinnen, Leonard Kuhrt, Benjamin Kohl, Patricia Bußmann, Carola Meier, Gundula Schulze-Tanzil, Wolfgang Ertel and Michal Jagielski

Cells 2023, 12(24), 2850; https://0-doi-org.brum.beds.ac.uk/10.3390/cells12242850 - 15 Dec 2023

Viewed by 986

Abstract

Osteoarthritis (OA) most frequently affects the knee joint and is associated with an elevated expression of cytokines and extracellular cartilage matrix (ECM), degrading enzymes such as matrix metalloproteinases (MMPs). Differences in gene expression of the intra-articularly located infrapatellar fat pad (IPFP) and other fatty tissue suggest its autonomous function, yet its role in OA pathogenesis remains unknown. Human IPFPs and articular cartilage were collected from OA patients undergoing total knee arthroplasty, and biopsies from the IPFP of healthy patients harvested during knee arthroscopy served as controls (CO). Isolated chondrocytes were co-cultured with either osteoarthritic (OA) or CO-IPFPs in a transwell system. Chondrocyte expression of MMP1, -3, -13, type 1 and 2 collagens, interleukin IL1β, IL6, IL10, and tumor necrosis factor TNFα was analyzed by RTD-PCR at day 0 and day 2, and TNFα secretion was analyzed by ELISA. The cytokine release in IPFPs was assessed by an array. Results: Both IPFPs (CO, OA) significantly reduced the expression of type 2 collagen and TNFα in chondrocytes. On the other hand, only CO-IPFP suppressed the expression of type 1 collagen and significantly induced the MMP13 expression. On the contrary, IL1β and IL6 were significantly induced when exposed to OA-IPFP. Conclusions: The partial loss of the suppressive effect on type 1 collagen gene expression found for OA-IPFP shows the pathological remodeling and dedifferentiation potential of the OA-IPFP on the chondrocytes. However, the significant suppression of TNFα implies that the OA- and CO-IPFP could also exhibit a protective role in the knee joint, preventing the progress of inflammation. Full article

(This article belongs to the Special Issue Cell and Molecular Causes of Joint Inflammation and Damage)

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17 pages, 3753 KiB

Open AccessArticle

Complement Proteins C5/C5a, Cathepsin D and Prolactin in Chondrocytes: A Possible Crosstalk in the Pathogenesis of Osteoarthritis

by Sandeep Silawal, Miriam Wagner, Dominik Roth, Thomas Bertsch, Silke Schwarz, Maximilian Willauschus, Markus Gesslein, Jakob Triebel and Gundula Schulze-Tanzil

Cells 2022, 11(7), 1134; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11071134 - 28 Mar 2022

Viewed by 2272

Abstract

Introduction: Both increased activity of the complement system (CS) and the role of the pituitary hormone prolactin (PRL) are implicated in osteoarthritis (OA) pathogenesis. Besides, Cathepsin D (CatD) activity is increased in the context of OA and can exert not only proteolytic but also non-proteolytic effects on cells. For the first time, possible crosstalk between two separate humoral systems: the CS and the PRL hormone systems in chondrocytes are examined together. Methods: Primary human articular chondrocytes (hAC) were stimulated with complement protein C5 (10 µg /mL), PRL (25 ng/mL), CatD (100 ng/mL), or anaphylatoxin C5a (25 ng/mL) for 24 h or 72 h, while unstimulated cells served as controls. In addition, co-stimulations of C5 or PRL with CatD were carried out under the same conditions. The influence of the stimulants on cell viability, cell proliferation, and metabolic activity of hAC, the chondrosarcoma cell line OUMS-27, and endothelial cells of the human umbilical cord vein (HUVEC) was investigated. Gene expression analysis of C5a receptor (C5aR1), C5, complement regulatory protein CD59, PRL, PRL receptor (PRLR), CatD, and matrix metal-loproteinases (MMP)-13 were performed using real-time PCR. Also, collagen type (Col) I, Col II, C5aR1, CD59, and PRL were detected on protein level using immunofluorescence labeling. Results: The stimulation of the hAC showed no significant impairment of the cell viability. C5, C5a, and PRL induced cell growth in OUMS-27 and HUVEC, but not in chondrocytes. CatD, as well as C5, significantly reduced the gene expression of CatD, C5aR1, C5, and CD59. PRLR gene expression was likewise impaired by C5, C5a, and PRL+CatD stimulation. On the protein level, CatD, as well as C5a, decreased Col II as well as C5aR1 synthesis. Conclusions: The significant suppression of the C5 gene expression under the influence of PRL+CatD and that of CD59 via PRL+/−CatD and conversely a suppression of the PRLR gene expression via C5 alone or C5a stimulation indicates an interrelation between the two mentioned systems. In addition, CatD and C5, in contrast to PRL, directly mediate possible negative feedback of their own gene expression. Full article

(This article belongs to the Special Issue Cell and Molecular Causes of Joint Inflammation and Damage)

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21 pages, 6941 KiB

Open AccessArticle

Single-Cell RNA-Seq Reveals Transcriptomic Heterogeneity and Post-Traumatic Osteoarthritis-Associated Early Molecular Changes in Mouse Articular Chondrocytes

by Aimy Sebastian, Jillian L. McCool, Nicholas R. Hum, Deepa K. Murugesh, Stephen P. Wilson, Blaine A. Christiansen and Gabriela G. Loots

Cells 2021, 10(6), 1462; https://0-doi-org.brum.beds.ac.uk/10.3390/cells10061462 - 10 Jun 2021

Cited by 39 | Viewed by 10120

Abstract

Articular cartilage is a connective tissue lining the surfaces of synovial joints. When the cartilage severely wears down, it leads to osteoarthritis (OA), a debilitating disease that affects millions of people globally. The articular cartilage is composed of a dense extracellular matrix (ECM) with a sparse distribution of chondrocytes with varying morphology and potentially different functions. Elucidating the molecular and functional profiles of various chondrocyte subtypes and understanding the interplay between these chondrocyte subtypes and other cell types in the joint will greatly expand our understanding of joint biology and OA pathology. Although recent advances in high-throughput OMICS technologies have enabled molecular-level characterization of tissues and organs at an unprecedented resolution, thorough molecular profiling of articular chondrocytes has not yet been undertaken, which may be in part due to the technical difficulties in isolating chondrocytes from dense cartilage ECM. In this study, we profiled articular cartilage from healthy and injured mouse knee joints at a single-cell resolution and identified nine chondrocyte subtypes with distinct molecular profiles and injury-induced early molecular changes in these chondrocytes. We also compared mouse chondrocyte subpopulations to human chondrocytes and evaluated the extent of molecular similarity between mice and humans. This work expands our view of chondrocyte heterogeneity and rapid molecular changes in chondrocyte populations in response to joint trauma and highlights potential mechanisms that trigger cartilage degeneration. Full article

(This article belongs to the Special Issue Cell and Molecular Causes of Joint Inflammation and Damage)

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Review

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37 pages, 1816 KiB

Open AccessReview

Chondrocyte Hypertrophy in Osteoarthritis: Mechanistic Studies and Models for the Identification of New Therapeutic Strategies

by Shikha Chawla, Andrea Mainardi, Nilotpal Majumder, Laura Dönges, Bhupendra Kumar, Paola Occhetta, Ivan Martin, Christian Egloff, Sourabh Ghosh, Amitabha Bandyopadhyay and Andrea Barbero

Cells 2022, 11(24), 4034; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11244034 - 13 Dec 2022

Cited by 18 | Viewed by 3477

Abstract

Articular cartilage shows limited self-healing ability owing to its low cellularity and avascularity. Untreated cartilage defects display an increased propensity to degenerate, leading to osteoarthritis (OA). During OA progression, articular chondrocytes are subjected to significant alterations in gene expression and phenotype, including a shift towards a hypertrophic-like state (with the expression of collagen type X, matrix metalloproteinases-13, and alkaline phosphatase) analogous to what eventuates during endochondral ossification. Present OA management strategies focus, however, exclusively on cartilage inflammation and degradation. A better understanding of the hypertrophic chondrocyte phenotype in OA might give new insights into its pathogenesis, suggesting potential disease-modifying therapeutic approaches. Recent developments in the field of cellular/molecular biology and tissue engineering proceeded in the direction of contrasting the onset of this hypertrophic phenotype, but knowledge gaps in the cause–effect of these processes are still present. In this review we will highlight the possible advantages and drawbacks of using this approach as a therapeutic strategy while focusing on the experimental models necessary for a better understanding of the phenomenon. Specifically, we will discuss in brief the cellular signaling pathways associated with the onset of a hypertrophic phenotype in chondrocytes during the progression of OA and will analyze in depth the advantages and disadvantages of various models that have been used to mimic it. Afterwards, we will present the strategies developed and proposed to impede chondrocyte hypertrophy and cartilage matrix mineralization/calcification. Finally, we will examine the future perspectives of OA therapeutic strategies. Full article

(This article belongs to the Special Issue Cell and Molecular Causes of Joint Inflammation and Damage)

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13 pages, 2203 KiB

Open AccessReview

Subacromial Bursa: A Neglected Tissue Is Gaining More and More Attention in Clinical and Experimental Research

by Franka Klatte-Schulz, Kathi Thiele, Markus Scheibel, Georg N. Duda and Britt Wildemann

Cells 2022, 11(4), 663; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11040663 - 14 Feb 2022

Cited by 12 | Viewed by 11055

Abstract

The subacromial bursa has long been demolded as friction-reducing tissue, which is often linked to shoulder pain and, therefore, partially removed during shoulder surgery. Currently, the discovery of the stem cell potential of resident bursa-derived cells shed a new light on the subacromial bursa. In the meanwhile, this neglected tissue is gaining more attention as to how it can augment the regenerative properties of adjacent tissues such as rotator cuff tendons. Specifically, the tight fibrovascular network, a high growth factor content, and the large progenitor potential of bursa-derived cells could complement the deficits that a nearby rotator cuff injury might experience due to the fact of its low endogenous regeneration potential. This review deals with the question of whether bursal inflammation is only a pain generator or could also be an initiator of healing. Furthermore, several experimental models highlight potential therapeutic targets to overcome bursal inflammation and, thus, pain. More evidence is needed to fully elucidate a direct interplay between subacromial bursa and rotator cuff tendons. Increasing attention to tendon repair will help to guide future research and answer open questions such that novel treatment strategies could harvest the subacromial bursa’s potential to support healing of nearby rotator cuff injuries. Full article

(This article belongs to the Special Issue Cell and Molecular Causes of Joint Inflammation and Damage)

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