Although the effects of mechanical loading on chondrocyte metabolic activities have been extensively characterized, the sequence of events through which extracellular mechanical signals are transduced into chondrocytes and ultimately modulate cell activities is not well understood. Here, studies were performed to map out the sequential intracellular signalling pathways through which compression-induced signals modulate aggrecan mRNA levels in bovine articular chondrocytes. Bovine articular cartilage explants were subjected to a compressive stress of 0.1MPa for 1h in the presence or absence of inhibitors or antagonists of the phosphoinositol and Ca2+/calmodulin signalling pathways in order to determine the roles of second messengers and effector molecules of these pathways in transducing the compression-induced signals. In the absence of the inhibitors, aggrecan mRNA levels were stimulated by compression 2–4-fold relative to levels in tare-loaded (see below) explants. Treatment of the explants with graded levels of the protein kinase C inhibitor chelerythrine or bisindolylmaleimide I, followed by 1h compressive loading, did not significantly alter the load-induced elevation of aggrecan mRNA levels. In contrast, thapsigargin, which depletes the Ins(1,4,5)P3-sensitive intracellular Ca2+ stores, completely blocked the load response without significantly altering aggrecan mRNA levels in tare-loaded explants. Similarly, antagonists of the Ca2+/calmodulin signalling pathway dose-dependently or completely blocked the load-response. The results obtained demonstrate that transduction of the compression-induced aggrecan mRNA-regulating signals requires Ins(1,4,5)P3- and Ca2+/calmodulin-dependent signalling processes in bovine articular chondrocytes.
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Research Article|
January 25 2002
myo-Inositol 1,4,5-trisphosphate and Ca2+/calmodulin-dependent factors mediate transduction of compression-induced signals in bovine articular chondrocytes
Wilmot B. VALHMU;
Wilmot B. VALHMU
1
∗Orthopedic Biosciences Laboratory, Department of Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, WI 53792, U.S.A.
1To whom correspondence should be addressed (e-mail valhmu@surgery.wisc.edu).
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Frank J. RAIA
Frank J. RAIA
†Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Columbia University, New York, NY 10032, U.S.A.
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Publisher: Portland Press Ltd
Received:
May 25 2001
Revision Received:
November 05 2001
Accepted:
November 16 2001
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2002
2002
Biochem J (2002) 361 (3): 689–696.
Article history
Received:
May 25 2001
Revision Received:
November 05 2001
Accepted:
November 16 2001
Citation
Wilmot B. VALHMU, Frank J. RAIA; myo-Inositol 1,4,5-trisphosphate and Ca2+/calmodulin-dependent factors mediate transduction of compression-induced signals in bovine articular chondrocytes. Biochem J 1 February 2002; 361 (3): 689–696. doi: https://doi.org/10.1042/bj3610689
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