UNASSIGNED: Chondrocytes are the sole cell type found in articular cartilage and are repeatedly subjected to mechanical loading in vivo. We hypothesized that physiological dynamic compression results in changes in energy metabolism to produce proteins for maintenance of the pericellular and extracellular matrices. The objective of this study was to develop an in-depth understanding for the short term (<30min) chondrocyte response to sub-injurious, physiological compression by analyzing metabolomic profiles for @entity1 chondrocytes harvested from femoral heads of osteoarthritic donors. Cell-seeded agarose constructs were randomly assigned to experimental groups, and dynamic compression was applied for 0, 15, or 30min. Following dynamic compression, metabolites were extracted and detected by HPLC-MS. Untargeted analyzes examined changes in global metabolomics profiles and targeted analysis examined the expression of specific metabolites related to central energy metabolism. We identified hundreds of metabolites that were regulated by applied compression, and we report the detection of 16 molecules not found in existing metabolite databases. We observed @entity1 -specific mechanotransduction with aging @entity734 . Targeted studies found a transient increase in the ratio of @entity1110 + to @entity1110 and an initial decrease in the ratio of @entity3006 to @entity3007 , suggesting a flux of energy into the @entity2974 cycle. By characterizing metabolomics profiles of primary chondrocytes in response to applied dynamic compression, this study provides insight into how OA chondrocytes respond to mechanical load. These results are consistent with increases in glycolytic energy utilization by mechanically induced signaling, and add substantial new data to a complex picture of how chondrocytes transduce mechanical loads.

Mechanotransduction in primary XXXX osteoarthritic chondrocytes is mediated by metabolism of energy, lipids, and amino acids.

@entity1 :: ('9606', 'Species') :: ['human', 'patient'] @entity3007 :: ('MESH:D006160', 'Chemical') :: ['GTP'] @entity2974 :: ('CHEBI:30956', 'Chemical') :: ['TCA'] @entity1110 :: ('MESH:D009249', 'Chemical') :: ['NADPH', 'NADP'] @entity3006 :: ('MESH:D006153', 'Chemical') :: ['GDP'] @entity734 :: ('MESH:D019966', 'Disease') :: ['dependence']
@entity1 :: (9606,Species) :: ['human']
