TY - JOUR
T1 - Mechanical loading of articular cartilage reduces IL-1-induced enzyme expression
AU - Torzilli, P. A.
AU - Bhargava, M.
AU - Chen, C. T.
N1 - Funding Information:
Support for this study was made possible by Grant Number AR45748 (PAT) from the National Institutes of Health–National Institute of Arthritis and Musculoskeletal and Skin Diseases . Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH-NIAMS. This investigation was conducted in a facility constructed with support from Research Facilities Improvement Program Grant Number C06-RR12538-01 from the National Center for Research Resources, National Institutes of Health . The authors thank Natalie Casemyr and Valerie Wolfe for expert technical help in performing, collecting, and assembling the mRNA data.
PY - 2011/10
Y1 - 2011/10
N2 - Objective: Exposure of articular cartilage to interleukin-1 (IL-1) results in increased synthesis of matrix degrading enzymes. Previously mechanical load applied together with IL-1 stimulation was found to reduce aggrecan cleavage by ADAMTS-4 and 5 and MMP-1, -3, -9, and -13 and reduce proteoglycan loss from the extracellular matrix. To further delineate the inhibition mechanism the gene expression of ADAMTS-4 and 5; MMP-1, -3, -9, and -13; and TIMP-1, -2, and -3 were measured. Design: Mature bovine articular cartilage was stimulated with a 0.5 MPa compressive stress and 10 ng/ml of IL-1α for 3 days and then allowed to recover without stimulation for 1 additional day. The media was assayed for proteoglycan content on a daily basis, while chondrocyte gene expression (mRNA) was measured during stimulation and 1 day of recovery. Results: Mechanical load alone did not change the gene expression for ADAMTS, MMP, or TIMP. IL-1 caused an increase in gene expression for all enzymes after 1 day of stimulation while not affecting the TIMP levels. Load applied together with IL-1 decreased the expression levels of ADAMTS-4 and -5 and MMP-1 and -3 and increased TIMP-3 expression. Conclusions: A mechanical load appears to modify cartilage degradation by IL-1 at the cellular level by reducing mRNA.
AB - Objective: Exposure of articular cartilage to interleukin-1 (IL-1) results in increased synthesis of matrix degrading enzymes. Previously mechanical load applied together with IL-1 stimulation was found to reduce aggrecan cleavage by ADAMTS-4 and 5 and MMP-1, -3, -9, and -13 and reduce proteoglycan loss from the extracellular matrix. To further delineate the inhibition mechanism the gene expression of ADAMTS-4 and 5; MMP-1, -3, -9, and -13; and TIMP-1, -2, and -3 were measured. Design: Mature bovine articular cartilage was stimulated with a 0.5 MPa compressive stress and 10 ng/ml of IL-1α for 3 days and then allowed to recover without stimulation for 1 additional day. The media was assayed for proteoglycan content on a daily basis, while chondrocyte gene expression (mRNA) was measured during stimulation and 1 day of recovery. Results: Mechanical load alone did not change the gene expression for ADAMTS, MMP, or TIMP. IL-1 caused an increase in gene expression for all enzymes after 1 day of stimulation while not affecting the TIMP levels. Load applied together with IL-1 decreased the expression levels of ADAMTS-4 and -5 and MMP-1 and -3 and increased TIMP-3 expression. Conclusions: A mechanical load appears to modify cartilage degradation by IL-1 at the cellular level by reducing mRNA.
KW - Articular cartilage < Tissue
KW - Chondrocytes < Cells
KW - Degradative enzymes < Cytokines and growth factors
KW - Interleukins < Cytokines and growth factors
KW - Mechanobiology < Diagnostics
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U2 - 10.1177/1947603511407484
DO - 10.1177/1947603511407484
M3 - Article
C2 - 22039566
AN - SCOPUS:84863171942
SN - 1947-6035
VL - 2
SP - 364
EP - 373
JO - Cartilage
JF - Cartilage
IS - 4
ER -