RESUMEN

Rheumatoid arthritis (RA) is an inflammatory disease with joint dysfunction following cartilage degradation. The level of lysophosphatidic acid (LPA) has been reported to be augmented in human synovial fluid from patients with RA. However, it remains to be elucidated whether LPA participates in cartilage destruction. In the present study, we have demonstrated that the production of promatrix metalloproteinases (proMMPs)-1 and -3 was augmented along with an increase of extracellular signal-regulated kinase (ERK)1/2 phosphorylation through LPA receptor 1 (LPAR1) in human synovial fibroblasts. These results suggest that LPA transcriptionally increases MMP production by the activation of an LPAR1/ERK1/2 signal pathway in human synovial fibroblasts. Thus, LPA is likely to be a pathological candidate for cartilage degradation in RA.

Asunto(s)

Fibroblastos/enzimología , Lisofosfolípidos/farmacología , Metaloproteinasa 1 de la Matriz/biosíntesis , Metaloproteinasa 3 de la Matriz/biosíntesis , Membrana Sinovial/enzimología , Células Cultivadas , Relación Dosis-Respuesta a Droga , Fibroblastos/efectos de los fármacos , Expresión Génica , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/fisiología , Metaloproteinasa 1 de la Matriz/genética , Metaloproteinasa 3 de la Matriz/genética , Membrana Sinovial/efectos de los fármacos