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. JunDdeficiencysignificantlyincreasedbonemassandtrabecularnumber.ThisbonemassenhancementwasduetoJunD 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 massoccurredinJunD-deficientmice.Inapathologicalconditionrelevanttopostmenopausalosteoporosis,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 suppressboneformationandtoenhanceboneresorption.J.Cell.Biochem.103:1037-1045,2008. 2008Wiley-Liss,Inc.