Lysophosphatidic Acid Augments the Gene Expression and Production of Matrix Metalloproteinases-1 and -3 in Human Synovial Fibroblasts in Vitro.

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 (LPAR ₁ ) in human synovial fibroblasts. These results suggest that LPA transcriptionally increases MMP production by the activation of an LPAR ₁ /ERK1/2 signal pathway in human synovial fibroblasts. Thus, LPA is likely to be a pathological candidate for cartilage degradation in RA.