Background/Purpose Bone erosion is an important feature of rheumatoid arthritis (RA) that frequently results in lifelong crippling. The receptor activator of NFkB ligand (RANKL)/osteoprotegerin (OPG)/RANK receptor (RANK) system triggers bone loss in arthritis and is activated by proinflammatory cytokines such as TNFa. Prolactin (PRL), the hormone essential for lactation, may protect against bone loss in RA. PRL stimulates bone formation and frequently increases in the circulation of patients with RA. Moreover, hyperprolactinemia reduces chondrocyte apoptosis, proinflammatory cytokine expression, pannus formation, joint swelling, and pain in adjuvant-induced arthritic (AIA) rats (Adan et al., J Clin Invest 123:3902, 2013). Here, we investigate whether eliciting hyperprolactinemia before or after inducing AIA reduces the systemic levels of TNFa and inhibits the expression of the RANKL/OPG/RANK system and bone erosion in arthritic ankle joints. 

Methods Progression of inflammation (joint swelling) was analyzed in rats implanted or not with osmotic minipumps delivering PRL beginning 3 days before of 15 days after the injection of Complete Freunds’ adjuvant (CFA). At maximal inflammation (21 days post CFA), bone erosion was evaluated histochemically, RANKL/OPG/RANK, TNFa, and PRL receptor (PRLR) mRNA levels in arthritic joints were quantified by qRT-PCR; and systemic TNFa protein levels were determined by ELISA. 

Results Expression of the PRLR was significantly elevated in the joints of AIA rats. Treatment with PRL before or after inducing AIA reduced local (hind paw) expression and serum levels of TNFa. Moreover, PRL reduced the AIA-induced increase of RANKL and RANK expression in joints, but did not modify that of the RANKL inhibitor OPG. Consistent with these findings, treatment with PRL before inflammation onset significantly reduced the AIA-induced loss of cortical and trabecular bone.

Conclusion PRL-induced down-regulation of TNFa/RANKL/RANK expression may protect against bone destruction in arthritis, supporting the therapeutic potential of hyperprolactinemia in RA. Funded by UNAM grant IN200312.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/prolactin-reduces-bone-erosion-in-adjuvant-induced-arthritis/