Runx2 determines bone maturity and turnover rate in postnatal bone development and is involved in bone loss in estrogen deficiency.
Runx2 is an essential transcription factor for osteoblast differentiation. However, the functions of Runx2 in postnatal bone development remain to be clarified. Introduction of dominant-negative (dn)-Runx2 did not inhibit Col1a1 and osteocalcin expression in mature osteoblastic cells. In transgenic mice that expressed dn-Runx2 in osteoblasts, the trabecular bone had increased mineralization, increased volume, and features of compact bone, and the expression of major bone matrix protein genes was relatively maintained. After ovariectomy, neither osteolysis nor bone formation was enhanced and bone was relatively conserved. In wild-type mice, Runx2 was strongly expressed in immature osteoblasts but downregulated during osteoblast maturation. These findings indicate that the maturity and turnover rate of bone are determined by the level of functional Runx2 and Runx2 is responsible for bone loss in estrogen deficiency, but that Runx2 is not essential for maintenance of the expression of major bone matrix protein genes in postnatal bone development and maintenance.
Maruyama
Zenjiro
Z
Department of Cell Biology, Unit of Basic Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Yoshida
Carolina A
CA
Furuichi
Tatsuya
T
Amizuka
Norio
N
Ito
Masako
M
Fukuyama
Ryo
R
Miyazaki
Toshihiro
T
Kitaura
Hideki
H
Nakamura
Kouhei
K
Fujita
Takashi
T
Kanatani
Naoko
N
Moriishi
Takeshi
T
Yamana
Kei
K
Liu
Wenguang
W
Kawaguchi
Hiroshi
H
Nakamura
Kozo
K
Komori
Toshihisa
T
D000818:Animals; D001846:Bone Development / Q000502:physiology*; D001862:Bone Resorption / Q000378:metabolism*; D001842:Bone and Bones / Q000378:metabolism*; D002460:Cell Line; D050659:Core Binding Factor Alpha 1 Subunit / Q000502:physiology*; D004967:Estrogens / Q000172:deficiency*; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000378:metabolism
D050659:Core Binding Factor Alpha 1 Subunit; D004967:Estrogens; C493716:Runx2 protein, mouse