Mechanotransduction via integrins and interleukin-4 results in altered aggrecan and matrix metalloproteinase 3 gene expression in normal, but not osteoarthritic, human articular chondrocytes.

摘要: Objective. To determine molecular events in the regulation of messenger RNA (mRNA) cartilage matrix molecules and proteases by mechanical stimulation chondrocytes from normal human articular to ascertain whether similar regulatory systems are present osteoarthritic (OA) cartilage. Methods. Chondrocytes extracted macroscopically microscopically OA were mechanically stimulated presence or absence GRGDSP GRADSP oligopeptides, neutralizing interleukin-4 (IL-4) antibodies, gadolinium, apamin. The relative levels mRNA for aggrecan, tenascin, metalloproteinase 1 (MMP-1), MMP-3, tissue inhibitor metalloproteinases (TIMP-1) determined semiquantitative reverse transcription‐polymerase chain reaction at several time points up 24 hours poststimulation, using GAPDH as a control. Results. Normal showed an increase aggrecan decrease MMP-3 within hour following stimulation, with return baseline hours. These changes blocked GRGDSP, IL-4 but unaffected In contrast, isolated no change stimulation. MMP-1, TIMP-1 unaltered chondrocytes. Conclusion. Mechanical vitro results increased decreased mRNA. transduction process involves integrins, stretch-activated ion channels, IL-4. This chondroprotective response is absent Abnormalities mechanotransduction leading aberrant chondrocyte activity diseased may be important progression OA.