scholarly journals HIF-1α-induced HSP70 regulates anabolic responses in articular chondrocytes under hypoxic conditions

2014 ◽  
Vol 32 (8) ◽  
pp. 975-980 ◽  
Author(s):  
Shinji Tsuchida ◽  
Yuji Arai ◽  
Kenji A. Takahashi ◽  
Tsunao Kishida ◽  
Ryu Terauchi ◽  
...  
Keyword(s):  
Articular Chondrocytes ◽  
Hypoxic Conditions

scholarly journals Molecular and Cellular Effects of Chemical Chaperone—TUDCA on ER-Stressed NHAC-kn Human Articular Chondrocytes Cultured in Normoxic and Hypoxic Conditions

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 878
Author(s):  
Magdalena Kusaczuk ◽  
Monika Naumowicz ◽  
Rafał Krętowski ◽  
Bartosz Cukierman ◽  
Marzanna Cechowska-Pasko
Keyword(s):  
Er Stress ◽  
Articular Chondrocytes ◽  
Potential Candidate ◽  
Chemical Chaperone ◽  
Cellular Effects ◽  
Chop Expression ◽  
Hypoxic Conditions ◽  
Stressed Cells ◽  
Apoptotic Activity ◽  
Potential Therapeutics

Osteoarthritis (OA) is considered one of the most common arthritic diseases characterized by progressive degradation and abnormal remodeling of articular cartilage. Potential therapeutics for OA aim at restoring proper chondrocyte functioning and inhibiting apoptosis. Previous studies have demonstrated that tauroursodeoxycholic acid (TUDCA) showed anti-inflammatory and anti-apoptotic activity in many models of various diseases, acting mainly via alleviation of endoplasmic reticulum (ER) stress. However, little is known about cytoprotective effects of TUDCA on chondrocyte cells. The present study was designed to evaluate potential effects of TUDCA on interleukin-1β (IL-1β) and tunicamycin (TNC)-stimulated NHAC-kn chondrocytes cultured in normoxic and hypoxic conditions. Our results showed that TUDCA alleviated ER stress in TNC-treated chondrocytes, as demonstrated by reduced CHOP expression; however, it was not effective enough to prevent apoptosis of NHAC-kn cells in either normoxia nor hypoxia. However, co-treatment with TUDCA alleviated inflammatory response induced by IL-1β, as shown by down regulation of Il-1β, Il-6, Il-8 and Cox2, and increased the expression of antioxidant enzyme Sod2. Additionally, TUDCA enhanced Col IIα expression in IL-1β- and TNC-stimulated cells, but only in normoxic conditions. Altogether, these results suggest that although TUDCA may display chondoprotective potential in ER-stressed cells, further analyses are still necessary to fully confirm its possible recommendation as potential candidate in OA therapy.

Growth factor regulation of intracellular pH homeostasis under hypoxic conditions in isolated equine articular chondrocytes

2012 ◽  
Vol 31 (2) ◽  
pp. 197-203 ◽  
Author(s):  
Peter I. Milner ◽  
Hannah C. Smith ◽  
Rebecca Robinson ◽  
Robert J. Wilkins ◽  
John S. Gibson
Keyword(s):  
Growth Factor ◽  
Intracellular Ph ◽  
Articular Chondrocytes ◽  
Ph Homeostasis ◽  
Hypoxic Conditions ◽  
Growth Factor Regulation

Haem oxygenase-1 induction reverses the actions of interleukin-1β on hypoxia-inducible transcription factors and human chondrocyte metabolism in hypoxia

2013 ◽  
Vol 125 (2) ◽  
pp. 99-108 ◽  
Author(s):  
Victoria Clérigues ◽  
Christopher L. Murphy ◽  
Maria Isabel Guillén ◽  
Maria José Alcaraz
Keyword(s):  
Articular Chondrocytes ◽  
Protoporphyrin Ix ◽  
Interleukin 1Β ◽  
Protective Effects ◽  
Protein Levels ◽  
Hypoxic Conditions ◽  
Cobalt Protoporphyrin ◽  
Haem Oxygenase ◽  
Oa Chondrocytes ◽  
Factor Α

HO-1 (haem oxygenase-1) catalyses the degradation of haem and possesses anti-inflammatory and cytoprotective properties. The role of inflammatory mediators in the pathogenesis of OA (osteoarthritis) is becoming increasingly appreciated. In the present study, we investigated the effects of HO-1 induction in OA and healthy HACs (human articular chondrocytes) in response to inflammatory cytokine IL-1 β (interleukin-1β) under hypoxic conditions. Hypoxia was investigated as it is a more physiological condition of the avascular cartilage. Hypoxic signalling is mediated by HIFs (hypoxia-inducible factors), of which there are two main isoforms, HIF-1α and HIF-2α. Normal and OA chondrocytes were stimulated with IL-1β. This cytokine suppresses HO-1 expression and exerts both catabolic and anti-anabolic effects, while increasing HIF-1α and suppressing HIF-2α protein levels in OA chondrocytes in hypoxia. Induction of HO-1 by CoPP (cobalt protoporphyrin IX) reversed these IL-1β actions. The hypoxia-induced anabolic pathway involving HIF-2α, SOX9 [SRY (sex determining region Y)-box 9] and COL2A1 (collagen type II α1) was suppressed by IL-1β, but importantly, levels were restored by HO-1 induction, which down-regulated TNFα (tumour necrosis factor α), MMP (matrix metalloproteinase) activity and MMP-13 protein levels. Depletion of HO-1 using siRNA (small interfering RNA) abolished the CoPP effects, further demonstrating that these were due to HO-1. The results of the present study reveal the different mechanisms by which HO-1 exerts protective effects on chondrocytes in physiological levels of hypoxia.

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.

Collagen degradation products modulate matrix metalloproteinase expression in cultured articular chondrocytes

2005 ◽  
Vol 24 (1) ◽  
pp. 63-70 ◽  
Author(s):  
M. Fichter ◽  
U. Körner ◽  
J. Schömburg ◽  
L. Jennings ◽  
A. A. Cole ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Articular Chondrocytes ◽  
Degradation Products ◽  
Collagen Degradation ◽  
Collagen Degradation Products
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