ATP modulates load-inducible IL-1β, COX 2, and MMP-3 gene expression in human tendon cells
Tendon cells receive mechanical signals from the load bearing matrices. The response to mechanical stimulation is crucial for tendon function. However, overloading tendon cells may deteriorate extracellular matrix integrity by activating intrinsic factors such as matrix metalloproteinases (MMPs) tha...
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Published in | Journal of cellular biochemistry Vol. 89; no. 3; pp. 556 - 562 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
01.06.2003
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Subjects | |
Online Access | Get full text |
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Summary: | Tendon cells receive mechanical signals from the load bearing matrices. The response to mechanical stimulation is crucial for tendon function. However, overloading tendon cells may deteriorate extracellular matrix integrity by activating intrinsic factors such as matrix metalloproteinases (MMPs) that trigger matrix destruction. We hypothesized that mechanical loading might induce interleukin‐1beta (IL‐1β) in tendon cells, which can induce MMPs, and that extracellular ATP might inhibit the load‐inducible gene expression. Human tendon cells isolated from flexor digitorum profundus tendons (FDPs) of four patients were made quiescent and treated with ATP (10 or 100 μM) for 5 min, then stretched equibiaxially (1 Hz, 3.5% elongation) for 2 h followed by an 18‐h‐rest period. Stretching induced IL‐1β, cyclooxygenase 2 (COX 2), and MMP‐3 genes but not MMP‐1. ATP reduced the load‐inducible gene expression but had no effect alone. A medium change caused tendon cells to secrete ATP into the medium, as did exogenous UTP. The data demonstrate that mechanical loading induces ATP release in tendon cells and stimulates expression of IL‐1β, COX 2, and MMP‐3. Load‐induced endogenous IL‐1β may trigger matrix remodeling or a more destructive pathway(s) involving IL‐1β, COX 2, and MMP‐3. Concomitant autocrine and paracrine release of ATP may serve as a negative feedback mechanism to limit activation of such an injurious pathway. Attenuation or failure of this negative feedback mechanism may result in the progression to tendinosis. © 2003 Wiley‐Liss, Inc. |
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Bibliography: | istex:7A150791552D8E221AFBBEDD13F1A9ED4C90F579 ArticleID:JCB10534 NIH-NHLBI - No. HL62584 Flexcell International Corp NIH - No. AR 38121; No. AR 45833 ark:/67375/WNG-Q16JD1XL-B Hunt Foundation, Merck, Inc. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0730-2312 1097-4644 |
DOI: | 10.1002/jcb.10534 |