Conditional Inactivation of Noggin in the Postnatal Skeleton Causes Osteopenia
Conditional Inactivation of Noggin in the Postnatal Skeleton Causes Osteopenia
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DOI：
10.1210/en.2011-1604
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发表时间：
2012-04-01
期刊：
影响因子：
4.8
通讯作者：
Zanotti, Stefano
中科院分区：
文献类型：
--
作者：
Canalis, Ernesto;Brunet, Lisa J.;Zanotti, Stefano
Noggin是骨形态发生蛋白（BMP）的拮抗剂，其过度表达可导致成骨细胞发生抑制和骨减少。Noggin的全局失活导致严重的发育缺陷和产前死亡，但Noggin的条件失活对出生后骨骼的影响尚不清楚。为了研究noggin在成骨细胞中的功能，我们通过将noggin条件小鼠与骨钙素启动子（Oc-Cre）控制下表达Cre重组酶的小鼠配对，产生了组织特异性的无noggin小鼠，其中noggin等位基因的两侧是loxP序列。Noggin条件null小鼠表现出体重下降、股骨长度缩短和广泛性骨质减少。1月龄和3月龄Noggin条件阴性小鼠股骨远端骨组织形态学和微结构分析显示，由于骨小梁数量减少，骨体积减少。椎体微结构证实了Noggin条件缺失小鼠的骨质减少。1月龄雄性Noggin条件无效小鼠的破骨细胞数量增加，3月龄小鼠的骨形成增加，但雌性小鼠的骨重塑没有增加。综上所述，Noggin失活导致骨减少，这表明BMP过量对骨骼有害，或者Noggin在骨骼稳态中具有BMP独立的作用。（内分泌学153:1616-1626,2012）
Noggin is an antagonist of bone morphogenetic proteins (BMP), and its overexpression causes suppressed osteoblastogenesis and osteopenia. Global inactivation of Noggin results in severe developmental defects and prenatal lethality, but the consequences of the conditional inactivation of Noggin on the postnatal skeleton are not known. To study the function of noggin in osteoblasts, we generated tissue-specific null Noggin mice by mating Noggin conditional mice, where the Noggin allele is flanked by loxP sequences, with mice expressing the Cre recombinase under the control of the osteocalcin promoter (Oc-Cre). Noggin conditional null mice exhibited decreased weight, shortened femoral length, and generalized osteopenia. Bone histomorphometric and microarchitectural analyses of distal femurs revealed decreased bone volume due to a reduced number of trabeculae in 1- and 3-month-old Noggin conditional null mice. Vertebral microarchitecture confirmed the osteopenia observed in Noggin conditional null mice. Osteoclast number was increased in 1-month-old male Noggin conditional null mice, and bone formation was increased in 3-month-old mice, but female mice did not exhibit increased bone remodeling. In conclusion, Noggin inactivation causes osteopenia, suggesting that BMP in excess have a detrimental effect on bone or that noggin has a BMP-independent role in skeletal homeostasis. (Endocrinology 153: 1616-1626, 2012)