Cyclic mechanical stress induces extracellular matrix degradation in cultured chondrocytes via gene expression of matrix metalloproteinases and interleukin-1.
To clarify the mechanism of cartilage degradation induced by mechanical stress, we investigated the influence of cyclic tension force (CTF) on the metabolism of cultured chondrocytes. The chondrocytes were exposed to CTF using a Flexercell strain unit. Five or 15 kPa of high frequency CTF significantly inhibited the syntheses of DNA, proteoglycan, collagen, and protein. Fifteen kPa of high frequency CTF induced the expression of interleukin-1 (IL-1), matrix metalloproteinase (MMP)-2 and -9 mRNA, and increased the production of pro- and active-MMP-9. The degradation of proteoglycan was inhibited by and MMP inhibitor, indicating that MMPs are involved in the degradation of proteoglycans induced by high frequency CTF. Moreover, reducing the frequency of CTF from high to low decreased the inhibition of proteoglycan synthesis. These findings suggest that the CTF frequency is one of the key determinants of chondrocyte metabolism. Low magnitude CTF, whether high or low frequency, did not cause the gene expression of cartilage degradation factors, suggesting that this CTF magnitude causes only minor changes in the cartilage matrix. High magnitude and frequency CTF caused the gene expression of IL-1 and MMP-9, followed by increases in the production of MMP-2 and -9 proteins, suggesting that excessive and continuous cyclic mechanical stress induces the production of IL-1 and MMP-9, resulting in cartilage degradation.
Fujisawa
T
T
Department of Biochemistry and Molecular Dentistry, Okayama University Dental School, Okayama, 700-8525, Japan.
Hattori
T
T
Takahashi
K
K
Kuboki
T
T
Yamashita
A
A
Takigawa
M
M
D000818:Animals; D001483:Base Sequence; D002356:Cartilage / Q000201:enzymology / Q000378:metabolism*; D002460:Cell Line; D003094:Collagen / Q000096:biosynthesis / Q000378:metabolism; D017364:Collagenases / Q000235:genetics*; D017931:DNA Primers; D004261:DNA Replication; D005109:Extracellular Matrix / Q000201:enzymology / Q000378:metabolism*; D018093:Gelatinases / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D006868:Hydrolysis; D007375:Interleukin-1 / Q000235:genetics*; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011509:Proteoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D013314:Stress, Mechanical; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics
D017931:DNA Primers; D007375:Interleukin-1; D011509:Proteoglycans; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D003094:Collagen; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9