Bone morphogenetic protein type IA receptor signaling regulates postnatal osteoblast function and bone remodeling
Bone morphogenetic protein type IA receptor signaling regulates postnatal osteoblast function and bone remodeling
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DOI：
10.1074/jbc.m404222200
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发表时间：
2004-06-25
影响因子：
4.8
通讯作者：
Behringer, RR
中科院分区：
文献类型：
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作者：
Mishina, Y;Starbuck, MW;Behringer, RR
骨形态发生蛋白（BMP）在胚胎发育的各个方面发挥作用，包括骨骼发生。然而，它们出生后的生物学功能却不太清楚。为了研究骨形态发生蛋白在骨重建过程中的作用，我们对小鼠体内编码骨形态发生蛋白IA型受体的Bmpr1a进行了出生后成骨细胞特异性破坏。突变小鼠在出生后6个月内比对照组小。观察到不规则钙化和低骨量，但成骨细胞数量正常。突变成骨细胞在培养中形成矿化结节的能力严重降低。有趣的是，由于骨吸收减少（由骨转换减少证明），老年突变小鼠的骨量增加。卵巢切除术后，突变小鼠丢失更多的骨，可能是由于成骨细胞功能下降，无法克服卵巢切除术诱导的骨吸收。在老年小鼠骨器官培养中，腺病毒Cre重组酶对Bmpr1a基因的消融消除了BMP 4对骨细胞骨吸收所必需的溶酶体酶表达的刺激作用。这些结果证明了由BMPRIA（BMP的IA型受体）在成骨细胞中介导的BMP信号传导对于骨重建的重要和年龄依赖性作用。
Bone morphogenetic proteins (BMPs) function during various aspects of embryonic development including skeletogenesis. However, their biological functions after birth are less understood. To investigate the role of BMPs during bone remodeling, we generated a postnatal osteoblast-specific disruption of Bmpr1a that encodes the type IA receptor for BMPs in mice. Mutant mice were smaller than controls up to 6 months after birth. Irregular calcification and low bone mass were observed, but there were normal numbers of osteoblasts. The ability of the mutant osteoblasts to form mineralized nodules in culture was severely reduced. Interestingly, bone mass was increased in aged mutant mice due to reduced bone resorption evidenced by reduced bone turnover. The mutant mice lost more bone after ovariectomy likely resulting from decreased osteoblast function which could not overcome ovariectomy-induced bone resorption. In organ culture of bones from aged mice, ablation of the Bmpr1a gene by adenoviral Cre recombinase abolished the stimulatory effects of BMP4 on the expression of lysosomal enzymes essential for osteoclastic bone resorption. These results demonstrate essential and age-dependent roles for BMP signaling mediated by BMPRIA ( a type IA receptor for BMP) in osteoblasts for bone remodeling.