Advanced glycation end products increases matrix metalloproteinase-1, -3, and -13, and TNF-alpha in human osteoarthritic chondrocytes.
We investigated the effects of advanced glycation end products (AGE) which accumulate in articular cartilage with age in human osteoarthritic chondrocytes. We found AGE-BSA significantly increased MMP-1, -3, and -13, and TNF-alpha in a dose-dependent manner. AGE-BSA-stimulated JNK, p38, and ERK and NF-kappaB activity. The stimulatory effect of AGE-BSA on MMP-1, -3, and -13 were reversed by treatment with specific JNK, p38 inhibitors, suggesting JNK and p38 are involved in AGE-BSA-induced MMPs and TNF-alpha. We also observed that NF-kappaB is involved in AGE-BSA-induced TNF-alpha. Pretreatment with soluble receptor for AGE (sRAGE) also reduced AGE-stimulated MMPs and TNF-alpha, implicating the involvement of receptor for AGE (RAGE). In conclusion, accumulation of AGE may have a role in the development of osteoarthritis by increasing MMP-1, -3, and -13, and TNF-alpha.
Nah
Seong-Su
SS
Division of Allergy and Rheumatology, Department of Internal Medicine, College of Medicine, University of Ulsan, Asan Medical Center, 388-1, Pungnap-dong, Songpa-gu, Seoul 138-736, Republic of Korea.
Choi
In-Young
IY
Yoo
Bin
B
Kim
Yong Gil
YG
Moon
Hee-Bom
HB
Lee
Chang-Keun
CK
D000368:Aged; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism*; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1