PROLACTIN INHIBITS CHONDROCYTE APOPTOSIS IN THE ADJUVANT-INDUCED MODEL OF RHEUMATOID ARTHRITIS IN RATS

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 112-141-Hypothalamus-Pituitary Development & Biology
Basic/Clinical
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-139
Maria Norma Adan*1, Maria Guadalupe Ledesma-Colunga1, Fernando López-Barrera1, Andres Quintanar-Stephano2, Stephanie Thebault1, Gonzalo Martinez de la Escalera1 and Carmen Clapp1
1National University of Mexico (UNAM), Querétaro, Mexico, 2Universidad Autónoma de Aguascalientes, Aguascalientes, Mexico
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). Natural chondrocyte survival factors have the potential to be developed for therapeutic application in RA. PRL frequently increases in the circulation of patients with RA and protects chondrocytes against apoptosis induced by TNF-α, IL-1β, and IFN-γ in vivo and in vitro. Given that these cytokines can cause apoptosis-mediated cartilage loss in RA, we investigated whether PRL reduces the apoptosis of chondrocytes in the adjuvant-induced RA model in rats. Osmotic minipumps delivering PRL or subcutaneous tablets releasing haloperidol (Hal), a dopamine D2 receptor antagonist that causes hyperprolactinemia, were implanted 3 days before the injection of complete Freund’s adjuvant (CFA) and resulted in elevated serum PRL levels throughout the experiment. CFA injection stimulated the expression of caspase-3, bax, and p53 in ankle joints and promoted the apoptosis of chondrocytes in the knee cartilage as revealed by TUNEL and active caspase-3 immunostaining. PRL or Hal infusion lowered CFA-induced expression of proapoptotic mediators and chondrocyte apoptosis. Moreover, when the osmotic minipumps delivering PRL were placed 15 days after the injection of CFA, i.e., when joint swelling is evident, higher levels of serum PRL correlated with reduced expression of proapoptotic mediators and with the lowering of chondrocyte apoptosis. These findings reveal the protective effect of PRL against inflammation-induced cartilage loss and the therapeutic potential of hyperprolactinemia to reduce permanent joint damage in RA.

Nothing to Disclose: MNA, MGL, FL, AQ, ST, GM, CC

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: PAPIIT-UNAM grant 200312-3.