The Japan Society for Menopause and Women’s Health

Journal of the Japan Society for Menopause and Women’s Health

V0l.18-1 V0l.18-2 V0l.19-1 vol.19-2 vol.20-1
vol.20-2 vol.20-3 vol.21-1 vol.21-2 vol.22-1

V0l.22-1　

Review article The Role of Dickkopf-4 in Pathogenesis of Postmenopausal Osteoporosis

Shiro Hiramitsu

Department of Comprehensive Reproductive Medicine, Tokyo Medical and Dental University,

Summery
The Dickkopf family of proteins comprises of 4 members (Dkk1/2/3/4) that are known to modulate Wnt/β-catenin signaling. Although the effects of Dkk1 on the Wnt/β-catenin signaling pathway, which is activated during bone formation, have been well studied, little is known about the effects of Dkk4. Therefore, to evaluate the role of Dkk4 in osteoblastogenesis, we conducted the following experiments. We used a mouse osteoblastic cell line MC3T3-E1, Dkk4 of which was reduced by siRNA. Our results showed that suppression of Dkk4 expression using siRNA in MC3T3-E1 promotes osteoblast proliferation and differentiation, while suppressing apoptosis. Decreased Dkk4 expression also leads to the up-regulation of β-catenin/TCF activity and Wnt-target genes. Additionally, to determine whether Dkk4 was associated with increased bone metabolism in postmenopausal osteoporosis, a cross-sectional observational study was conducted in 51 peri- and postmenopausal women (60.2 ± 15.3 years; Mean ± SD). The serum levels of Dkk1/3/4 were compared with bone metabolism markers. The serum levels of Dkk4 are associated with the expression of bone metabolism markers in pre- and postmenopausal women. Our findings reveal that Dkk4 inhibits bone formation through Wnt/β-catenin signaling and is related to the increased bone turnover in pre- and postmenopausal women.