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

• Published in: Biological & pharmaceutical bulletin Vol. 44; no. 1; pp. 131 - 135
• Main Authors: Mizuno, Koji, Komiya, Michika, Okuyama, Katsuki, Imada, Keisuke, Sato, Takashi
• Format: Journal Article
• Language: English; Japanese
• Published: Japan The Pharmaceutical Society of Japan 01.01.2021; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: Cartilage; cartilage destruction; Extracellular signal-regulated kinase; extracellular signal-regulated kinase (ERK)1/2; Fibroblasts; Gene expression; human synovial fibroblast; Inflammatory diseases; Kinases; Lysophosphatidic acid; Matrix metalloproteinase; Phosphorylation; Rheumatoid arthritis; Synovial fluid; Transcription; matrix metalloproteinase; human synovial fibroblast; lysophosphatidic acid; cartilage destruction; rheumatoid arthritis; extracellular signal-regulated kinase (ERK)1/2
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b20-00518

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.