Assorted effects of TGFbeta and chondroitinsulfate on p38 and ERK1/2 activation levels in human articular chondrocytes stimulated with LPS

Autor: M. Huettinger, A. Zemann, R. Schabus, S. Marlovits, R. Cowburn, J. Holzmann, N. Brandl
Rok vydání: 2005
Předmět:
MAPK/ERK pathway
Cartilage
Articular
Lipopolysaccharides
medicine.medical_specialty
Cell signaling
LPS
Chondroitinsulfate
medicine.medical_treatment
Biomedical Engineering
Gene Expression
p38
p38 Mitogen-Activated Protein Kinases
Chondrocyte
Chondrocytes
Downregulation and upregulation
Rheumatology
Transforming Growth Factor beta
Internal medicine
Matrix Metalloproteinase 13
medicine
Humans
Orthopedics and Sports Medicine
Collagenases
Extracellular Signal-Regulated MAP Kinases
Cells
Cultured
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
biology
ERK1/2
Chondroitin Sulfates
Transforming growth factor beta
Metalloproteinases
TGF
Enzyme Activation
Endocrinology
Cytokine
medicine.anatomical_structure
biology.protein
Matrix Metalloproteinase 2
Matrix Metalloproteinase 3
Signal transduction
Transforming growth factor
Signal Transduction
Zdroj: Osteoarthritis and cartilage. 14(6)
ISSN: 1063-4584
Popis: Summary Objectives Inadequate cellular response of chondrocytes to stress frequently terminates in osteoarthritis (OA). Adequate response is fundamentally modulated by concerted cytokine signaling events, directing degradation and synthesis of cartilage on articular surfaces where and whenever necessary. Transforming growth factor (TGF)β is a prominent mediator in cartilage anabolism, although particular catabolic activities are occasionally reported. Clearly, before the TGFβ signal gets through to the gene regulatory machinery, cross talk with modulators occurs. Method We tested the hypothesis whether chondroitinsulfate (CS) modulates cell signaling. TGFβ and/or soluble CS was added to human articular chondrocytes (HACs) and activation of p38 and extracellular signal related kinase (ERK)1/2 was determined by immunoblot analysis. Expression levels of mRNA of matrix metalloproteinase (MMP)-2, -3 and -13 were determined by real-time polymerase chain reaction (PCR). Results No significant effects were observed unless cells were stimulated with lipopolysaccharide (LPS), invigorating catabolic metabolism in chondrocytes. LPS effects, however, were profoundly modulated by TGFβ, CS and both applied in combination. Most prominent, the silencing of p38 stress signal by CS was superimposable to that of TGFβ. Phospho-ERK1/2 levels were raised by TGFβ three-fold over LPS induced levels. In contrast, CS treatment, alone or combined with TGFβ, reduced phosphorylation significantly below LPS induced levels. Finally, suppression of LPS induced MMP-13 mRNA levels resulted with CS. Conclusion Soluble CS modulates signaling events in chondrocytes concurrent with MMP-13 down regulation. The effects observed suggest a feedback signaling mechanism cross talking with TGFβ-signal pathways and may serve an explanation, on the cellular level, for the beneficial effects found in clinical studies with pharmacologic application of CS.
Databáze: OpenAIRE
Externí odkaz: