Estrogen specifically stimulates expression and production of osteoprotegerin from rheumatoid synovial fibroblasts

Makoto Mitani; Yasushi Miura; Ryuichi Saura; Atsushi Kitagawa; Taihei Fukuyama; Akira Hashiramoto; Shunichi Shiozawa; Masahiro Kurosaka; Shinichi Yoshiya

Estrogen specifically stimulates expression and production of osteoprotegerin from rheumatoid synovial fibroblasts

Int J Mol Med. 2005 May;15(5):827-32.

Authors

Makoto Mitani¹, Yasushi Miura, Ryuichi Saura, Atsushi Kitagawa, Taihei Fukuyama, Akira Hashiramoto, Shunichi Shiozawa, Masahiro Kurosaka, Shinichi Yoshiya

Affiliation

¹ Department of Orthopaedic Surgery, Kobe University, Graduate School of Medicine, Kobe 650-0017, Japan.

PMID: 15806305

Abstract

We studied the effects of estrogen on human fibroblast-like synovial cells in rheumatoid arthritis (RA-FLS) focusing on receptor activator of NF-kappaB ligand (RANKL) and its decoy receptor osteoprotegerin (OPG), the osteoclast formation and function regulators that have a substantial role in bone erosion of RA. Estrogen influences osteoporosis and the onset of RA clinically. The cellular responses of RA-FLS to estrogen are initiated via two high-affinity estrogen receptors (ERs). Culture of RA-FLS in the presence of 10(-6) M 17beta-estradiol (E2) increased expression of estrogen receptor (ER)-alpha, but not ER-beta. OPG mRNA expression was significantly increased, whereas RANKL mRNA was unaffected. E2 treatment also significantly increased the amount of OPG released in the culture supernatant. The increase of OPG and ER-alpha was specifically antagonized by the pure estrogen antagonist ICI 182780. Tamoxifen, a selective ER moderator, did not increase OPG. The results indicate that estrogen stimulates secretion of OPG from RA-FLS by acting on ER-alpha, which likely prevents bone erosion in RA.

MeSH terms

Arthritis, Rheumatoid / metabolism*
Carrier Proteins / biosynthesis
Cells, Cultured
Estradiol / analogs & derivatives*
Estradiol / pharmacology*
Estrogen Receptor Modulators / pharmacology
Estrogen Receptor alpha / biosynthesis
Estrogen Receptor beta / biosynthesis
Estrogens / pharmacology*
Fibroblasts / drug effects*
Fibroblasts / metabolism
Fulvestrant
Glycoproteins / biosynthesis*
Humans
Membrane Glycoproteins / biosynthesis
Osteoprotegerin
RANK Ligand
RNA, Messenger / biosynthesis
Receptor Activator of Nuclear Factor-kappa B
Receptors, Cytoplasmic and Nuclear / biosynthesis*
Receptors, Tumor Necrosis Factor / biosynthesis*
Synovial Membrane / metabolism*
Tamoxifen / pharmacology
Up-Regulation

Substances

Carrier Proteins
Estrogen Receptor Modulators
Estrogen Receptor alpha
Estrogen Receptor beta
Estrogens
Glycoproteins
Membrane Glycoproteins
Osteoprotegerin
RANK Ligand
RNA, Messenger
Receptor Activator of Nuclear Factor-kappa B
Receptors, Cytoplasmic and Nuclear
Receptors, Tumor Necrosis Factor
TNFRSF11A protein, human
TNFRSF11B protein, human
TNFSF11 protein, human
Tamoxifen
Fulvestrant
Estradiol