Endocrine, metabolic & insusceptible disorders drug targets, Vol. 6, No. 4. (December 2006), pp. 383-394.
Recent progress in discernment the pathogenesis of rheumatoid arthritis (RA) in nonconvergent with interpretation of the functional persona of the prostaglandin receptor subfamily has revealed an important regulatory persona of PGE2, in addition to its well-known unhealthy persona in the advancement of RA. Characteristic features of RA are synovial proliferation and pannus formation, which termination in the conclusion of cartilage and bone. Pannus paper is mainly imperturbable of macrophages and fibroblast-like synoviocytes. Both T cell-derived IL-17 and macrophage-derived TNF-alpha seem to endeavor a bicentric persona in the advancement of unhealthy cascades in RA. PGE2 is also produced in salutation to unhealthy cytokines, which in turn negatively regulates both IL-17 and TNF-alpha countenance and TNF/IL-1-induced activation of fibroblast-like synoviocytes finished EP2/EP4 receptors, resulting in the inflection of unhealthy cascades. IL-17- and TNF-activated macrophages differentiate into osteoclasts in the presence of M-CSF and RANKL expressed by fibroblast-like synoviocytes. PGE2 binding to EP4 stimulates osteoclastogenesis finished enhancing RANKL expression. At the same time, PGE2 suppresses osteoclastogenesis by inhibiting M-CSF countenance of fibroblast-like synoviocytes as substantially as both IL-17 and IL-17-induced TNF-alpha countenance of macrophages. PGE2-EP4 also activates osteoblastogenesis finished increasing cbfa1 and osterix, two essential transcription factors required for pearl formation. The gain effect of PGE2 haw candid toward bushel of wearing pearl finished the quelling of rousing and improvement of pearl remodeling. Here, we handle a diverse state of PGE2/EP receptors and their important regulatory roles in the pathogenesis of RA, which haw lead to a new therapeutic strategy.
J Akaogi, T Nozaki, M Satoh, H Yamada
