P146 Dynamic Compression of Chondrocytes Induces a Rho Kinase-Dependent Reorganization of the Actin Cytoskeleton

Haudenschild, Dominik R.; Nguyen, Brenda; Dooley, Z.; Chen, J.; Mak, Yunxian; Colwell, Christopher S.; D'Lima, Darryl D.; Lotz, Martin

doi:10.1016/s1063-4584(07)60598-6

Cited by 11 publications

(19 citation statements)

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“…standing, walking, running, etc.). Chondrocytes and other mammalian cells sense and respond to these mechanical stimuli through biochemical and biological outputs, but the intracellular pathways behind chondrocyte mechanotransduction remain unclear [4-6]. …”

Section: Introductionmentioning

confidence: 99%

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

Zignego

Hilmer

June

2015

Journal of Biomechanics

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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 (<30 min.) chondrocyte response to sub-injurious, physiological compression by analyzing metabolomic profiles for human 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 30 minutes. Following dynamic compression, metabolites were extracted and detected by HPLC-MS. Untargeted analyses 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 patient-specific mechanotransduction with aging dependence. Targeted studies found a transient increase in the ratio of NADP+ to NADPH and an initial decrease in the ratio of GDP to GTP, suggesting a flux of energy into the TCA 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.

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Section: Introductionmentioning

confidence: 99%

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

Zignego

Hilmer

June

2015

Journal of Biomechanics

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“…Primary chondrocytes and BMSCs were isolated from human total knee replacement patients utilizing institutional review board-approved deidentified waste tissues as previously described. [17][18][19] Briefly, cartilage was dissected from the bone and digested overnight with collagenase to release chondrocytes. Bone marrow was washed with buffered saline, strained through a 70-mm filter to remove clotted blood and bone chips, centrifuged to remove fat, then layered on a Percoll cushion.…”

Section: Primary Human Cell Isolation and Culturementioning

confidence: 99%

“…19,21,22 Each alginate disc contained approximately 66,000 cells and weighed 66 -4 mg, which was equivalent in volume and cell number the combined weight of 3 beads (65 -3 mg). To confirm that the alginate material properties were sufficient to transmit the nominal compressive strain to the cell cytosol, the stiffness of the alginate was estimated from the slope of the equilibrium stress versus strain curves between 2% and 20% strain, as gels were subjected to unconfined compression at 3% strain intervals.…”

Section: Three-dimensional Culture In Alginate Hydrogelsmentioning

confidence: 99%

Identification of a 3Kbp Mechanoresponsive Promoter Region in the Human Cartilage Oligomeric Matrix Protein Gene

Amanatullah

Hecht

et al. 2012

Tissue Engineering Part A

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“…Haudenschild et al (2008) investigated the effect of both dynamic tensile and compressive loading on uncommitted mesenchymal stem cells and performed microarray analyses to determine if these cells could distinguish between compression induced pressure and tension induced distortion. They reported distinct gene expression patterns that were directly related to conformational changes in cell shape and volume.…”

Section: Compressive Forcesmentioning

confidence: 99%

Musculoskeletal mechanobiology: Interpretation by external force and engineered substratum

McCullen

Haslauer

Loboa

2010

Journal of Biomechanics

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P146 Dynamic Compression of Chondrocytes Induces a Rho Kinase-Dependent Reorganization of the Actin Cytoskeleton

Cited by 11 publications

References 0 publications

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

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

Identification of a 3Kbp Mechanoresponsive Promoter Region in the Human Cartilage Oligomeric Matrix Protein Gene

Musculoskeletal mechanobiology: Interpretation by external force and engineered substratum

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