JunD suppresses bone formation and contributes to low bone mass induced by estrogen depletion.
JunD is an activator protein-1 (AP-1) component though its function in skeletal system is still not fully understood. To elucidate the role of JunD in the regulation of bone metabolism, we analyzed JunD-deficient mice. JunD deficiency significantly increased bone mass and trabecular number. This bone mass enhancement was due to JunD deficiency-induced increase in bone formation activities in vivo. Such augmentation of bone formation was associated with simultaneous increase in bone resorption while the former was dominant over the latter as accumulation of bone mass occurred in JunD-deficient mice. In a pathological condition relevant to postmenopausal osteoporosis, ovariectomy reduced bone mass in wild type (WT) mice as known before. Interestingly, JunD deficiency suppressed ovariectomy-induced increase in bone resorption and kept high bone mass. In addition, JunD deficiency also enhanced new bone formation after bone marrow ablation. Examination of molecular bases for these observations revealed that JunD deficiency enhanced expression levels of c-jun, fra-1, and fra-2 in bone in conjunction with elevated expression levels of runx2, type I collagen, and osteocalcin. Thus, JunD is involved in estrogen depletion-induced osteopenia via its action to suppress bone formation and to enhance bone resorption.
Kawamata
Aya
A
Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, 101-0062, Tokyo, Japan.
Izu
Yayoi
Y
Yokoyama
Haruna
H
Amagasa
Teruo
T
Wagner
Erwin F
EF
Nakashima
Kazuhisa
K
Ezura
Yoichi
Y
Hayata
Tadayoshi
T
Noda
Masaki
M
D000818:Animals; D015519:Bone Density / Q000502:physiology*; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D001862:Bone Resorption / Q000378:metabolism / Q000503:physiopathology; D001842:Bone and Bones / Q000378:metabolism*; D004967:Estrogens / Q000172:deficiency / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010012:Osteogenesis / Q000502:physiology*; D010052:Ovariectomy; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000502:physiology*
D019485:Bone Morphogenetic Proteins; D004967:Estrogens; D016755:Proto-Oncogene Proteins c-jun