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New Advances in Osteoarthritis: Molecular Perspective

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 (31 August 2024) | Viewed by 4991

Special Issue Editor


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Guest Editor
Department of Anatomy, University of Tartu, Ravila 19, 50411 Tartu, Estonia
Interests: osteoarthritis; biomarker; cartilage intermediate layer proteins (CILP); electron microscopy; immunohistochemistry; molecular pathology

Special Issue Information

Dear Colleagues,

One of the most common joint diseases is osteoarthritis, which occurs primarily in elderly people, but due to obesity, the incidence of osteoarthritis has also increased among young people. Although the causes of osteoarthritis are still largely unclear, thanks to molecular research, it is understood that changes at the molecular level contribute to the disease. Cartilage intermediate layer proteins (CILP) are now recognized as one of the important cartilage structural molecules involved in the development of OA. The identification of new biomarkers, molecular and gene expression processes would be a major step forward in the diagnosis and treatment of osteoarthritis. It is not known which factors trigger the pathogenetic processes, and researchers should pay attention to finding target molecules that would enable the diagnosis of early starting processes in the joints and slow down or stop their development.

This Special Issue is focused on osteoarthritis and will publish original articles as well as reviews that present novel molecular, pathological and pathophysiological mechanisms.

Dr. Marina Aunapuu
Guest Editor

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Keywords

  • animal models
  • biomarkers
  • CILP
  • chondrocytes
  • electron microscopy
  • extracellular matrix
  • gene expression
  • immunohistochemistry
  • mechanisms
  • molecular biology
  • osteoarthritis
  • pathology
  • pericellular matrix
  • synovial membrane

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Published Papers (3 papers)

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Research

19 pages, 4231 KiB  
Article
Immune System-Related Plasma Pathogenic Extracellular Vesicle Subpopulations Predict Osteoarthritis Progression
by Xin Zhang, Sisi Ma, Syeda Iffat Naz, Erik J. Soderblom, Vaibhav Jain, Constantin Aliferis and Virginia Byers Kraus
Int. J. Mol. Sci. 2024, 25(23), 12504; https://doi.org/10.3390/ijms252312504 - 21 Nov 2024
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Abstract
Certain molecules found on the surface or within the cargo of extracellular vesicles (EVs) are linked to osteoarthritis (OA) severity and progression. We aimed to identify plasma pathogenic EV subpopulations that can predict knee radiographic OA (rOA) progression. We analyzed the mass spectrometry-based [...] Read more.
Certain molecules found on the surface or within the cargo of extracellular vesicles (EVs) are linked to osteoarthritis (OA) severity and progression. We aimed to identify plasma pathogenic EV subpopulations that can predict knee radiographic OA (rOA) progression. We analyzed the mass spectrometry-based proteomic data of plasma EVs and synovial fluid (SF) EVs from knee OA patients (n = 16, 50% female). The identified surface markers of interest were further evaluated in plasma EVs from an independent cohort of knee OA patients (n = 30, 47% female) using flow cytometry. A total of 199 peptides with significant correlation between plasma and SF EVs were identified. Of these, 41.7% were linked to immune system processes, 15.5% to inflammatory responses, and 16.7% to the complement system. Crucially, five previously identified knee rOA severity-indicating surface markers—FGA, FGB, FGG, TLN1, and AMBP—were confirmed on plasma EV subpopulations in an independent cohort. These markers’ baseline frequencies on large plasma EVs predicted rOA progression with an AUC of 0.655–0.711. Notably, TLN1 was expressed in OA joint tissue, whereas FGA, FGB, FGG, and AMBP were predominantly liver derived. These surface markers define specific pathogenic EV subpopulations, offering potential OA prognostic biomarkers and novel therapeutic targets for disease modification. Full article
(This article belongs to the Special Issue New Advances in Osteoarthritis: Molecular Perspective)
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18 pages, 16396 KiB  
Article
Degradation of Proteoglycans and Collagen in Equine Meniscal Tissues
by Julia Dubuc, Melodie Jil Schneider, Valerie Dubuc, Helene Richard, Maxime Pinsard, Stephane Bancelin, Francois Legare, Christiane Girard and Sheila Laverty
Int. J. Mol. Sci. 2024, 25(12), 6439; https://doi.org/10.3390/ijms25126439 - 11 Jun 2024
Viewed by 1393
Abstract
Investigate meniscal extracellular matrix degradation. Equine menisci (n = 34 from 17 horses) were studied. Site-matched sections were cut and scored from three regions (ROIs; n = 102) and stained for histology, proteoglycan (safranin O and fast green), aggrecan, and collagen cleavage [...] Read more.
Investigate meniscal extracellular matrix degradation. Equine menisci (n = 34 from 17 horses) were studied. Site-matched sections were cut and scored from three regions (ROIs; n = 102) and stained for histology, proteoglycan (safranin O and fast green), aggrecan, and collagen cleavage (NITEGE, DIPEN, and C1,2C antibodies, respectively). Picrosirius red and second harmonic generation microscopy were performed to investigate collagen ultrastructure. A total of 42 ROIs met the inclusion criteria and were included in the final analysis. The median (range) ROI histological score was 3 (0–9), providing a large spectrum of pathology. The median (range) proteoglycan score was 1 (0–3), representing superficial and central meniscal loss. The median (range) of DIPEN, NITEGE, and C1,2C scores was 1 (0–3), revealing immunostaining of the femoral and tibial surfaces. The proteoglycan scores exhibited significant positive associations with both histologic evaluation (p = 0.03) and DIPEN scores (p = 0.02). Additionally, a robust positive association (p = 0.007) was observed between the two aggrecanolysis indicators, NITEGE and DIPEN scores. A negative association (p = 0.008) was identified between NITEGE and histological scores. The C1,2C scores were not associated with any other scores. Picrosirius red and second harmonic generation microscopy (SHGM) illustrated the loss of the collagen matrix and structure centrally. Proteoglycan and collagen degradation commonly occur superficially in menisci and less frequently centrally. The identification of central meniscal proteoglycan and collagen degradation provides novel insight into central meniscal degeneration. However, further research is needed to elucidate the etiology and sequence of degradative events. Full article
(This article belongs to the Special Issue New Advances in Osteoarthritis: Molecular Perspective)
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13 pages, 1715 KiB  
Article
Fibrocyte Phenotype of ENTPD1+CD55+ Cells and Its Association with Pain in Osteoarthritic Synovium
by Maho Tsuchiya, Yoshihisa Ohashi, Kensuke Fukushima, Yusei Okuda, Arisa Suto, Takashi Matsui, Yoshio Kodera, Masashi Sato, Ayumi Tsukada, Gen Inoue, Masashi Takaso and Kentaro Uchida
Int. J. Mol. Sci. 2024, 25(7), 4085; https://doi.org/10.3390/ijms25074085 - 6 Apr 2024
Cited by 1 | Viewed by 1642
Abstract
Osteoarthritis (OA) is a prevalent degenerative joint disorder characterized by cartilage erosion, structural changes, and inflammation. Synovial fibroblasts play a crucial role in OA pathophysiology, with abnormal fibroblastic cells contributing significantly to joint pathology. Fibrocytes, expressing markers of both hematopoietic and stromal cells, [...] Read more.
Osteoarthritis (OA) is a prevalent degenerative joint disorder characterized by cartilage erosion, structural changes, and inflammation. Synovial fibroblasts play a crucial role in OA pathophysiology, with abnormal fibroblastic cells contributing significantly to joint pathology. Fibrocytes, expressing markers of both hematopoietic and stromal cells, are implicated in inflammation and fibrosis, yet their marker and role in OA remain unclear. ENTPD1, an ectonucleotidase involved in purinergic signaling and expressed in specific fibroblasts in fibrotic conditions, led us to speculate that ENTPD1 plays a role in OA pathology by being expressed in fibrocytes. This study aimed to investigate the phenotype of ENTPD1+CD55+ and ENTPD1−CD55+ synovial fibroblasts in OA patients. Proteomic analysis revealed a distinct molecular profile in ENTPD1+CD55+ cells, including the upregulation of fibrocyte markers and extracellular matrix-related proteins. Pathway analysis suggested shared mechanisms between OA and rheumatoid arthritis. Correlation analysis revealed an association between ENTPD1+CD55+ fibrocytes and resting pain in OA. These findings highlight the potential involvement of ENTPD1 in OA pain and suggest avenues for targeted therapeutic strategies. Further research is needed to elucidate the underlying molecular mechanisms and validate potential therapeutic targets. Full article
(This article belongs to the Special Issue New Advances in Osteoarthritis: Molecular Perspective)
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