The anti-angiogenesis mechanism of Geniposide on rheumatoid arthritis is related to the regulation of PTEN.

Abstract

Rheumatoid arthritis (RA) is a systemic immune disease characterized by joint inflammation and pannus. The nascent pannus contributes to synovial hyperplasia, cartilage, and tissue damage in RA. This study aims to explore the therapeutic effect and potential mechanism of Geniposide (GE) on RA angiogenesis, involving the participation of phosphate and tension homology deleted on chromosome ten (PTEN) and downstream pathways. Clinical manifestations, synovial pathomorphology, microvessel density, and the level of angiogenesis-related factors were used to evaluate the therapeutic effect of GE on adjuvant-induced arthritis (AA) rats. The proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) indicate the degree of angiogenesis in vitro. Lentivirus over-expression of PTEN was employed to elucidate the potential mechanism. The results showed that GE improved the degree of arthritis and angiogenesis in AA rats. The expression of PTEN was decreased significantly in vivo and in vitro, and over-expression of PTEN improved the biological function of HUVECs to inhibit angiogenesis. GE inhibited the proliferation, migration, and tubule formation of HUVECs and plays an anti-angiogenesis role in vitro. Mechanism study showed that PTEN expression was increased and p-PI3K and p-Akt expression was decreased with GE treatment. It suggests that GE up-regulated the expression of PTEN and inhibited the activation of PI3K-Akt signal, which plays a role in inhibiting angiogenesis in RA in vivo and in vitro.