Mineralocorticoid receptor function in bone metabolism and its role in glucocorticoid-induced osteopenia.
Although the mineralocorticoid receptor (MR) is expressed in osteoblasts and osteocytes and frequently co-localizes with the glucocorticoid receptors (GR), its pathophysiological functions in bone remain elusive. We report here that pharmacologic inhibition of MR function with eplerenone resulted in increased bone mass, with stimulation of bone formation and suppression of resorption, while specific genetic deletion of MR in osteoblast lineage cells had no effect. Further, treatment with eplerenone as well as specific deletion of MR in osteocytes ameliorated the cortical bone thinning caused by slow-release prednisolone pellets. Thus, MR may be involved in the deleterious effects of glucocorticoid excess on cortical bone.
Department of Bone and Joint Disease, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan.
Toshio
T
Fumoto
Department of Bone and Joint Disease, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan.
Kiyo-Aki
KA
Ishii
Medical Work-Life-Balance Center, Nagasaki University Hospital, Nagasaki 852-8501, Japan.
Masako
M
Ito
Department of Molecular Biology of the Cell I, German Cancer Center, Heidelberg, Germany.
Stefan
S
Berger
Department of Molecular Biology of the Cell I, German Cancer Center, Heidelberg, Germany.
Günther
G
Schütz
Department of Bone and Joint Disease, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan. Electronic address: kikeda@ncgg.go.jp.
Kyoji
K
Ikeda
D000818:Animals; D001851:Bone Diseases, Metabolic / Q000139:chemically induced* / Q000378:metabolism; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D000077545:Eplerenone; D005938:Glucocorticoids / Q000009:adverse effects*; D051379:Mice; D008815:Mice, Inbred Strains; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D010011:Osteocytes / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D011241:Prednisone / Q000009:adverse effects; D018161:Receptors, Mineralocorticoid / Q000502:physiology*; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology
D005938:Glucocorticoids; D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D000077545:Eplerenone; D011241:Prednisone
Eplerenone; Glucocorticoid; Mineralocorticoid receptor; Osteoporosis