High susceptibility to collagen-induced arthritis in mice with progesterone receptors selectively inhibited in osteoprogenitor cells

Abstract

Background: Progesterone receptor (PR) affects immunomodulation, and lack of PR in osteoprogenitor cells primarily affects pathways associated with immunomodulation, especially in males. In this study, we selectively deleted PR from osteoprogenitor cells using Prx1-Cre to evaluate the tissue-specific effects of PR on the pathegenesis of inflammatary arthritis (IA). Methods: Collagen-induced arthritis (CIA) was used as an IA animal model. Both male and female PR ΔPrx1 mice and their wild-type (WT) littermates were immunized with collagen II (CII) emulsified complete Freund's adjuvant (CFA). Joint erosion, inflammation, and cartilage damage were assessed using a semiquantitative histologic scoring system. Bone volume and erosions in knee and ankle joints were quantitated using microCT and histology. Results: Bone erosions developed in both paw joints in 37.5% and 41.7% of the WT and PR ΔPrx1 female mice and in 45.4 and 83.3% of the WT and PR ΔPrx1 male mice, respectively. Also, both joint damage and subchondral bone erosions were significantly more severe in male PRcKO-CIA mice than in male WT-CIA mice. Female PR ΔPrx1 mice also developed higher bone loss in the knee joints than the KO-normal or WT-CIA females although with less severity compared to the male mice. Conclusions: The presence of PR in osteoprogenitor cells decreased the development of collagen-induced arthritis and might help to explain the sex differences observed in human inflammatory arthritis.

Hormones and B-cell development in health and autoimmunity

“…In the same CIA model, it has also been reported that mice with deletion of a P4 receptor allele in osteoprogenitor cells (PR DPrx1-CIA) have a greater incidence of osteoarthritis. Male mice have lower bone mass in the legs and knees, a lower volume of subchondral trabecular bone and greater erosion and damage to the cartilage of the knee joint (167). Therefore, P4 plays a protective role in the manifestations of RA.…”