Schnurri-2 deficiency counteracts against bone loss induced by ovariectomy.
Schnurri (Shn)-2 is a transcriptional modulator of bone formation and bone resorption and its deficiency causes low turnover state with higher cancellous bone mass due to the defects in osteoclasts that exceeds the defects in osteoblasts in mice. We addressed whether such low turnover of bone remodeling in Shn2 deficiency may be modulated in the absence of estrogen that induces high turnover state in vivo. Ovariectomy reduced bone mass in wild type compared to sham operated control mice and such reduction in bone mass was also observed in Shn2 deficient mice. However, due to the high levels of basal bone mass in Shn2 deficient mice, the bone mass levels after ovariectomy were still comparable to sham operated wild-type mice. Analysis indicated that estrogen depletion increased bone resorption at similar levels in wild type and Shn2 deficient mice though the basal levels of osteoclast number was slightly lower in Shn2-deficient mice. In contrast, basal levels of bone marrow cell mineralization in cultures were low in Shn2-deficeint mice while estrogen depletion increased the mineralization levels to those that were comparable to sham wild type. This indicates that Shn2-deficient mice maintain bone mass at the levels comparable to wild-type sham mice even after ovariectomy-induced bone loss and this correlates with the high levels of mineralization activity in bone marrow cells after ovariectomy.
Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan. noda.mph@mri.tmd.ac.jp
Masashi
M
Nagao
Yoshitomo
Y
Saita
Ryo
R
Hanyu
Hiroaki
H
Hemmi
Takuya
T
Notomi
Tadayoshi
T
Hayata
Tetsuya
T
Nakamoto
Kazuhisa
K
Nakashima
Kazuo
K
Kaneko
Hisashi
H
Kurosawa
Shunsuke
S
Ishii
Yoichi
Y
Ezura
Masaki
M
Noda
D000818:Animals; D001862:Bone Resorption / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002113:Calcification, Physiologic; D002452:Cell Count; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000378:metabolism; D057075:Enzyme Assays; D005260:Female; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009929:Organ Size; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis; D010052:Ovariectomy
D004268:DNA-Binding Proteins; C490430:Hivep2 protein, mouse; D008156:Luciferases