IL-1beta regulates FHL2 and other cytoskeleton-related genes in human chondrocytes.
In osteoarthritis (OA), cartilage destruction is associated not only with an imbalance of anabolic and catabolic processes but also with alterations of the cytoskeletal organization in chondrocytes, although their pathogenetic origin is largely unknown so far. Therefore, we have studied possible effects of the proinflammatory cytokine IL-1beta on components of the cytoskeleton in OA chondrocytes on gene expression level. Using a whole genome array, we found that IL-1beta is involved in the regulation of many cytoskeleton-related genes. Apart from well-known cytoskeletal components, the expression and regulation of four genes coding for LIM proteins were shown. These four genes were previously undescribed in the chondrocyte context. Quantitative PCR analysis confirmed significant downregulation of Fhl1, Fhl2, Lasp1, and Pdlim1 as well as Tubb and Vim by IL-1beta. Inhibition of p38 mitogen-activated protein kinase (MAPK) by SB203580 counteracted the influence of IL-1beta on Fhl2 and Tubb expression, indicating partial involvement of this signaling pathway. Downregulation of the LIM-only protein FHL2 was confirmed additionally on the protein level. In agreement with these results, IL-1beta induced changes in the morphology of chondrocytes, the organization of the cytoskeleton, and the cellular distribution of FHL2. We conclude that L-1beta is involved in the regulation of various cytoskeletal components in human chondrocytes including the multifunctional protein FHL2. This might be relevant for the pathogenesis of OA.
Joos
Helga
H
Department of Orthopedics, University of Ulm, Ulm, Germany.
Albrecht
Wolfgang
W
Laufer
Stefan
S
Reichel
Heiko
H
Brenner
Rolf E
RE
D000368:Aged; D002356:Cartilage / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D048430:Cell Shape; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology; D003599:Cytoskeleton / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D060850:LIM-Homeodomain Proteins; D008875:Middle Aged; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010003:Osteoarthritis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D011725:Pyridines / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D004791:Enzyme Inhibitors; C105987:FHL2 protein, human; D018398:Homeodomain Proteins; D007093:Imidazoles; D053583:Interleukin-1beta; D060850:LIM-Homeodomain Proteins; D009124:Muscle Proteins; D011725:Pyridines; D014157:Transcription Factors; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580