Rapid regulation of collagen but not metalloproteinase 1, 3, 13, 14 and tissue inhibitor of metalloproteinase 1, 2, 3 expression in response to mechanical loading of cartilage explants in vitro.
This study analyzes the molecular response of articular chondrocytes to short-term mechanical loading with a special focus on gene expression of molecules relevant for matrix turnover. Porcine cartilage explants were exposed to static and dynamic unconfined compression and viability of chondrocytes was assessed to define physiologic loading conditions. Cell death in the superficial layer correlated with mechanical loading and occurred at peak stresses >or=6 MPa and a cartilage compression above 45%. Chondrocytes in native cartilage matrix responded to dynamic loading by rapid and highly specific suppression of collagen expression. mRNA levels dropped 11-fold (collagen 2; 6 MPa, P=0.009) or 14-fold (collagen 1; 3 and 6 MPa, P=0.009) while levels of aggrecan, tenascin-c, matrix metalloproteinases (MMP1, 3, 13, 14), and their inhibitors (TIMP1-3) did not change significantly. Thus, dynamic mechanical loading rapidly shifted the balance between collagen and aggrecan/tenascin/MMP/TIMP expression. A better knowledge of the chondrocyte response to mechanical stress may improve our understanding of mechanically induced osteoarthrits.
Fehrenbacher
Andreas
A
Department of Orthopaedic Surgery, University of Heidelberg, Abteilung Bereich Forschung, Schlierbacher Landstrasse 200a, 69118 Heidelberg, Germany.
Steck
Eric
E
Rickert
Markus
M
Roth
Wolfgang
W
Richter
Wiltrud
W
D053674:Aggrecans; D000818:Animals; D001696:Biomechanical Phenomena; D002356:Cartilage / Q000166:cytology / Q000502:physiology*; D016923:Cell Death; D002470:Cell Survival; D019902:Chondrocytes / Q000502:physiology; D003094:Collagen / Q000378:metabolism*; D017364:Collagenases / Q000235:genetics; D016326:Extracellular Matrix Proteins; D015870:Gene Expression; D066298:In Vitro Techniques; D037181:Lectins, C-Type; D053509:Matrix Metalloproteinase 13; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000235:genetics*; D011509:Proteoglycans / Q000235:genetics; D013552:Swine; D019063:Tenascin / Q000235:genetics; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics*
D053674:Aggrecans; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D011509:Proteoglycans; D019063:Tenascin; D019714:Tissue Inhibitor of Metalloproteinases; D003094:Collagen; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases