Candidate mediators of chondrocyte mechanotransduction via targeted and untargeted metabolomic measurements

Candidate mediators of chondrocyte mechanotransduction via targeted and untargeted metabolomic measurements

•SW1353 chondrocytes were mechanically compressed in a physiologically stiff 3D environment.•Following compression, untargeted and targeted metabolomics studies were performed.•This study identified candidate mediators of cellular mechanostransduction.•This research implicates central metabolism as...

Full description

Saved in:
Bibliographic Details
Published in:Archives of biochemistry and biophysics Vol. 545; pp. 116 - 123
Main Authors: Jutila, Aaron A., Zignego, Donald L., Hwang, Bradley K., Hilmer, Jonathan K., Hamerly, Timothy, Minor, Cody A., Walk, Seth T., June, Ronald K.
Format: Journal Article
Language:English
Published: United States Elsevier Inc 01-03-2014
Subjects:
Cartilage
Cell Line
Chondrocyte
Chondrocytes - cytology
Chondrocytes - metabolism
Humans
Joint biology
Mechanotransduction
Mechanotransduction, Cellular
Metabolome
Metabolomics
Metabolomics - methods
Osteoarthritis
Stress, Mechanical
Metabolomics
Cartilage
Mechanotransduction
Chondrocyte
Osteoarthritis
Joint biology
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:•SW1353 chondrocytes were mechanically compressed in a physiologically stiff 3D environment.•Following compression, untargeted and targeted metabolomics studies were performed.•This study identified candidate mediators of cellular mechanostransduction.•This research implicates central metabolism as a mechanosensitive pathway. Chondrocyte mechanotransduction is the process by which cartilage cells transduce mechanical loads into biochemical and biological signals. Previous studies have identified several pathways by which chondrocytes transduce mechanical loads, yet a general understanding of which signals are activated and in what order remains elusive. This study was performed to identify candidate mediators of chondrocyte mechanotransduction using SW1353 chondrocytes embedded in physiologically stiff agarose. Dynamic compression was applied to cell-seeded constructs for 0–30min, followed immediately by whole-cell metabolite extraction. Metabolites were detected via LC–MS, and compounds of interest were identified via database searches. We found several metabolites which were statistically different between the experimental groups, and we report the detection of 5 molecules which are not found in metabolite databases of known compounds indicating potential novel molecules. Targeted studies to quantify the response of central energy metabolites to compression found a transient increase in the ratio of NADP+ to NADPH and a continual decrease in the ratio of GDP to GTP, suggesting a flux of energy into the TCA cycle. These data are consistent with the remodeling of cytoskeletal components by mechanically induced signaling, and add substantial new data to a complex picture of how chondrocytes transduce mechanical loads.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
These authors made equal contributions to this work.
ISSN:0003-9861
1096-0384
DOI:10.1016/j.abb.2014.01.011