TY - JOUR
T1 - High susceptibility to collagen-induced arthritis in mice with progesterone receptors selectively inhibited in osteoprogenitor cells
AU - Liu, Lixian
AU - Jia, Junjing
AU - Jiang, Min
AU - Liu, Xueping
AU - Dai, Chenling
AU - Wise, Barton L.
AU - Lane, Nancy E.
AU - Yao, Wei
PY - 2020/7/2
Y1 - 2020/7/2
N2 - 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 PRΔPrx1 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 PRΔPrx1 female mice and in 45.4 and 83.3% of the WT and PRΔPrx1 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 PRΔPrx1 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.
AB - 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 PRΔPrx1 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 PRΔPrx1 female mice and in 45.4 and 83.3% of the WT and PRΔPrx1 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 PRΔPrx1 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.
KW - Inflammatory arthritis
KW - Osteoprogenitor cells
KW - Progesterone receptor
KW - Sex difference
KW - Susceptibility
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U2 - 10.1186/s13075-020-02242-8
DO - 10.1186/s13075-020-02242-8
M3 - Article
C2 - 32616012
AN - SCOPUS:85087657754
VL - 22
JO - Arthritis Research and Therapy
JF - Arthritis Research and Therapy
SN - 1478-6354
IS - 1
ER -