Arthritis Relief
Inflammatory joint diseases such as rheumatoid arthritis are often accompanied by cartilage loss, which is induced by the release of proinflammatory cytokines following chondrocyte apoptosis. Rheumatoid arthritis patients have increased levels of the hormone prolactin (PRL) in their blood. PRL is known modulator of the immune response with demonstrated anti-apoptotic activities. Furthermore, PRL and its receptor are both expressed by chondrocytes. Norma Adán and colleagues at Universidad Nacional Autónoma de México examine a role for PRL in prevention and treatment of joint damage. PRL was able to inhibit apoptosis in the presence of proinflammatory cytokines in both cultured chondrocytes and in the knee joints of rats. The authors also demonstrated that in a rat model of adjuvant-induced inflammatory arthritis, PRL treatment reduced bone erosion, joint swelling and pain. These results indicate that PRL may be an effective therapy for reducing permanent joint damage and inflammation in arthritis. The above image is a hemotoxylin and eosin stained section from the knee joint of a rat with adjuvant-induced arthritis. There is noticeable pannus formation and infiltration of inflammatory cells (purple staining in the upper right hand corner).
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Abstract
Chondrocytes are the only cells in cartilage, and their death by apoptosis contributes to cartilage loss in inflammatory joint diseases, such as rheumatoid arthritis (RA). A putative therapeutic intervention for RA is the inhibition of apoptosis-mediated cartilage degradation. The hormone prolactin (PRL) frequently increases in the circulation of patients with RA, but the role of hyperprolactinemia in disease activity is unclear. Here, we demonstrate that PRL inhibits the apoptosis of cultured chondrocytes in response to a mixture of proinflammatory cytokines (TNF-α, IL-1β, and IFN-γ) by preventing the induction of p53 and decreasing the BAX/BCL-2 ratio through a NO-independent, JAK2/STAT3–dependent pathway. Local treatment with PRL or increasing PRL circulating levels also prevented chondrocyte apoptosis evoked by injecting cytokines into the knee joints of rats, whereas the proapoptotic effect of cytokines was enhanced in PRL receptor–null (
Authors
Norma Adán, Jessica Guzmán-Morales, Maria G. Ledesma-Colunga, Sonia I. Perales-Canales, Andrés Quintanar-Stéphano, Fernando López-Barrera, Isabel Méndez, Bibiana Moreno-Carranza, Jakob Triebel, Nadine Binart, Gonzalo Martínez de la Escalera, Stéphanie Thebault, Carmen Clapp
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ISSN: 0021-9738 (print), 1558-8238 (online)