The influence of donor and hypoxic conditions on the assembly of cartilage matrix by osteoarthritic human articular chondrocytes on Hyalograft matrices

Biomaterials ◽  
2009 ◽  
Vol 30 (4) ◽  
pp. 535-540 ◽  
Author(s):  
Theoni Katopodi ◽  
Simon R. Tew ◽  
Peter D. Clegg ◽  
Timothy E. Hardingham
Keyword(s):  
Articular Chondrocytes ◽  
Cartilage Matrix ◽  
Human Articular Chondrocytes ◽  
Hypoxic Conditions

scholarly journals The Lysine Specific Demethylase-1 Negatively Regulates the COL9A1 Gene in Human Articular Chondrocytes

2020 ◽  
Vol 21 (17) ◽  
pp. 6322
Author(s):  
Anne-Laure Durand ◽  
Alexandre Dufour ◽  
Elisabeth Aubert-Foucher ◽  
Christine Oger-Desfeux ◽  
Marielle Pasdeloup ◽  
...  
Keyword(s):  
Articular Chondrocytes ◽  
Cartilage Matrix ◽  
Human Articular Chondrocytes ◽  
Collagen Molecule ◽  
Sequencing Analysis ◽  
Loss Of Function ◽  
Gene Encoding ◽  
Lysine Specific Demethylase ◽  
Function Strategy

Osteoarthritis (OA) is a degenerative disease of the joints which is associated with an impaired production of the cartilage matrix by the chondrocytes. Here, we investigated the role of Lysine-Specific Demethylase-1 (LSD1), a chromatin remodeling enzyme whose role in articular chondrocytes was previously associated with a catabolic activity and which is potentially involved during OA. Following a loss of function strategy and RNA sequencing analysis, we detail the genes which are targeted by LSD1 in human articular chondrocytes and identify COL9A1, a gene encoding the α1 chain of the cartilage-specific type IX collagen, as negatively regulated by LSD1. We show that LSD1 interacts with the transcription factor SOX9 and is recruited to the promoter of COL9A1. Interestingly, we observe that OA cartilage displays stronger LSD1 immunostaining compared with normal, and we demonstrate that the depletion of LSD1 in OA chondrocytes prevents the decrease in COL9A1 following Il-1β treatment. These results suggest LSD1 is a new regulator of the anabolic activity of articular chondrocytes potentially destabilizing the cartilage matrix, since it negatively regulates COL9A1, a gene encoding a crucial anchoring collagen molecule. This newly identified role played by LSD1 may thus participate in the alteration of the cartilage matrix during OA.

scholarly journals Human Articular Chondrocytes Retain Their Phenotype in Sustained Hypoxia While Normoxia Promotes Their Immunomodulatory Potential

Cartilage ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 467-479 ◽  
Author(s):  
Claire Mennan ◽  
John Garcia ◽  
Helen McCarthy ◽  
Sharon Owen ◽  
Jade Perry ◽  
...  
Keyword(s):  
Articular Chondrocytes ◽  
Quantitative Polymerase Chain Reaction ◽  
Growth Factor Receptor ◽  
Interferon Γ ◽  
Human Articular Chondrocytes ◽  
Pellet Culture ◽  
3 Dimensional ◽  
Hypoxic Conditions ◽  
Chondrogenic Phenotype ◽  
Immunomodulatory Potential

Objective To assess the phenotype of human articular chondrocytes cultured in normoxia (21% O2) or continuous hypoxia (2% O2). Design Chondrocytes were extracted from patients undergoing total knee replacement ( n = 5) and cultured in ~21% (normoxic chondrocytes, NC) and 2% (hypoxic chondrocytes, HC) oxygen in both monolayer and 3-dimensional (3D) pellet culture and compared with freshly isolated chondrocytes (FC). Cells were assessed by flow cytometry for markers indicative of mesenchymal stromal cells (MSCs), chondrogenic-potency and dedifferentiation. Chondrogenic potency and immunomodulatory gene expression was assessed in NC and HC by reverse transcription quantitative polymerase chain reaction. Immunohistochemistry was used to assess collagen II production following 3D pellet culture. Results NC were positive (>97%, n = 5) for MSC markers, CD73, CD90, and CD105, while HC demonstrated <90% positivity ( n = 4) and FC ( n = 5) less again (CD73 and CD90 <20%; CD105 <40%). The markers CD166 and CD151, indicative of chondrogenic de-differentiation, were significantly higher on NC compared with HC and lowest on FC. NC also produced the highest levels of CD106 and showed the greatest levels of IDO expression, following interferon-γ stimulation, indicating immunomodulatory potential. NC produced the highest levels of CD49c (>60%) compared with HC and FC in which production was <2%. Hypoxic conditions upregulated expression of SOX9, frizzled-related protein ( FRZB), fibroblast growth factor receptor 3 ( FGFR3), and collagen type II ( COL2A1) and downregulated activin receptor-like kinase 1 ( ALK1) in 3 out of 4 patients compared with normoxic conditions for monolayer cells. Conclusions Hypoxic conditions encourage retention of a chondrogenic phenotype with some immunomodulatory potential, whereas normoxia promotes dedifferentiation of chondrocytes toward an MSC phenotype with loss of chondrogenic potency but enhanced immunomodulatory capacity.

IL-10 overexpression differentially affects cartilage matrix gene expression in response to TNF-α in human articular chondrocytes in vitro

Cytokine ◽  
2008 ◽  
Vol 44 (3) ◽  
pp. 377-385 ◽  
Author(s):  
R.D. Müller ◽  
T. John ◽  
B. Kohl ◽  
A. Oberholzer ◽  
T. Gust ◽  
...  
Keyword(s):  
Gene Expression ◽  
Articular Chondrocytes ◽  
Cartilage Matrix ◽  
Human Articular Chondrocytes ◽  
Matrix Gene ◽  
Tnf Α

scholarly journals Interleukin-26 Has Synergistic Catabolic Effects with Palmitate in Human Articular Chondrocytes via the TLR4-ERK1/2-c-Jun Signaling Pathway

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2500
Author(s):  
Yi-Ting Chen ◽  
Chih-Chien Wang ◽  
Chia-Pi Cheng ◽  
Feng-Cheng Liu ◽  
Chian-Her Lee ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Inflammatory Arthritis ◽  
Articular Chondrocytes ◽  
Saturated Fatty Acids ◽  
Signal Transduction Pathway ◽  
Cartilage Degradation ◽  
Cartilage Matrix ◽  
Human Articular Chondrocytes ◽  
Cox 2 ◽  
Interleukin 26

The inflammatory cytokine interleukin-26 (IL-26) is highly expressed in the serum and synovial fluid of patients with inflammatory arthritis. The effect of IL-26 on human articular chondrocytes (HACs) remains unclear. Obesity is associated with disability of patients with rheumatoid arthritis and disease activity in those with ankylosing spondylitis. The saturated free fatty acid palmitate with IL-1β can synergistically induce catabolic effects in HACs. The aim of this study was to evaluate the effects of IL-26 and palmitate in HACs. In this study, palmitate markedly synergizes the IL-26-induced proinflammatory effects and matrix protease, including COX-2, IL-6, and MMP-1, in HACs via the toll-like receptor 4 (TLR4)-ERK1/2-c-Jun signal transduction pathway. The synergistic catabolic effects of palmitate and IL-26 were attenuated by inhibitors of TLR4 (TAK242), ERK1/2 (U0126), or c-Jun (SP600125) in HACs and cartilage matrix. In addition, metformin, a potential inhibitor of TLR4, also decreased expression of COX-2 and IL-6 induced by co-incubation with IL-26 and palmitate. IL-26 and palmitate synergistically induced expression of inflammatory and catabolic mediators, resulting in articular cartilage matrix breakdown. The present study also revealed a possible mechanism and therapeutic targets against articular cartilage degradation by increased saturated fatty acids in patients with inflammatory arthritis.

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