Osteoprotegerin reverses osteoporosis by inhibiting endosteal osteoclasts and prevents vascular calcification by blocking a process resembling osteoclastogenesis.
Osteoprotegerin reverses osteoporosis by inhibiting endosteal osteoclasts and prevents vascular calcification by blocking a process resembling osteoclastogenesis.
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DOI：
10.1084/jem.192.4.463
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发表时间：
2000-08-21
期刊：
影响因子：
--
通讯作者：
Simonet WS
中科院分区：
文献类型：
--
作者：
Min H;Morony S;Sarosi I;Dunstan CR;Capparelli C;Scully S;Van G;Kaufman S;Kostenuik PJ;Lacey DL;Boyle WJ;Simonet WS
在OPG转基因小鼠中，高水平的骨保护素（OPG）可引起骨质疏松症，伴有正常的牙齿萌出和骨伸长，并抑制骨膜内破骨细胞的发育和活性，但对骨膜破骨细胞没有抑制作用。我们证明，在OPG−/2小鼠中静脉注射重组OPG蛋白和转基因过表达OPG都能有效地挽救OPG缺陷小鼠的骨质疏松表型。然而，静脉注射重组OPG超过4周不能逆转在OPG−/−小鼠中观察到的动脉钙化。相比之下，从妊娠中期到成年期的转基因OPG确实阻止了OPG - / -小鼠动脉钙化的形成。虽然OPG在动脉中正常表达，但在野生型成年小鼠的动脉壁中未检测到OPG配体（OPGL）和NF-κB受体激活因子（RANK）。有趣的是，在OPG−/−小鼠的钙化动脉中检测到OPGL和RANK转录本。此外，RANK转录物的表达与多核破骨细胞样细胞的存在一致。这些结果表明，OPG/OPGL/RANK信号通路可能在病理和生理钙化过程中发挥重要作用。这些发现也可以解释在骨质疏松患者人群中观察到的高临床血管钙化发生率。
High systemic levels of osteoprotegerin (OPG) in OPG transgenic mice cause osteopetrosis with normal tooth eruption and bone elongation and inhibit the development and activity of endosteal, but not periosteal, osteoclasts. We demonstrate that both intravenous injection of recombinant OPG protein and transgenic overexpression of OPG in OPG−/2 mice effectively rescue the osteoporotic bone phenotype observed in OPG-deficient mice. However, intravenous injection of recombinant OPG over a 4-wk period could not reverse the arterial calcification observed in OPG−/− mice. In contrast, transgenic OPG delivered from mid-gestation through adulthood does prevent the formation of arterial calcification in OPG−/− mice. Although OPG is normally expressed in arteries, OPG ligand (OPGL) and receptor activator of NF-κB (RANK) are not detected in the arterial walls of wild-type adult mice. Interestingly, OPGL and RANK transcripts are detected in the calcified arteries of OPG−/− mice. Furthermore, RANK transcript expression coincides with the presence of multinuclear osteoclast-like cells. These findings indicate that the OPG/OPGL/RANK signaling pathway may play an important role in both pathological and physiological calcification processes. Such findings may also explain the observed high clinical incidence of vascular calcification in the osteoporotic patient population.
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影响因子：
15.3
作者：
Bunting, C H
通讯作者：
Bunting, C H
影响因子：
6.2
作者：
Morony, S;Capparelli, C;Dunstan, CR
通讯作者：
Dunstan, CR
影响因子：
4.1
作者：
Beamer, WG;Donahue, LR;Baylink, DJ
通讯作者：
Baylink, DJ
DOI：
10.1006/bbrc.1998.9788
发表时间：
1998-12-18
影响因子：
3.1
作者：
Nakagawa, N;Kinosaki, M;Higashio, K
通讯作者：
Higashio, K
影响因子：
9.2
作者：
Filvaroff, E;Derynck, R
通讯作者：
Derynck, R