Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist.
Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist.
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DOI：
10.1084/jem.20031454
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发表时间：
2004-03-15
期刊：
影响因子：
--
通讯作者：
Löwik CW
中科院分区：
文献类型：
--
作者：
van Bezooijen RL;Roelen BA;Visser A;van der Wee-Pals L;de Wilt E;Karperien M;Hamersma H;Papapoulos SE;ten Dijke P;Löwik CW
硬化症是一种骨骼疾病，其特征是由于成骨细胞活性增加而导致骨量增高，是由SOST基因产物硬化蛋白的丢失引起的。硬化蛋白在骨中的定位和作用机制尚不清楚，但有人推测它可能作为骨形态发生蛋白（BMP）拮抗剂。我们在这里发现SOST/sclerostin仅在小鼠和人骨的骨细胞中表达，并抑制小鼠成骨前细胞的分化和矿化（KS483）。尽管硬化蛋白具有BMP拮抗剂noggin的一些作用，但我们在这里表明它也具有明显不同的作用。与noggin相比，硬化蛋白不抑制KS483细胞的碱性磷酸酶（ALP）活性，也不拮抗bmp刺激的小鼠C2C12细胞的碱性磷酸酶活性。此外，在KS483细胞中，硬化蛋白对BMP刺激的Smad磷酸化和MSX-2和BMP反应元件报告因子构建的直接转录激活没有影响。其独特的定位和对成骨细胞的作用表明，硬化蛋白可能是先前提出的骨细胞衍生因子，在骨表面运输到成骨细胞并抑制骨形成。
Sclerosteosis, a skeletal disorder characterized by high bone mass due to increased osteoblast activity, is caused by loss of the SOST gene product, sclerostin. The localization in bone and the mechanism of action of sclerostin are not yet known, but it has been hypothesized that it may act as a bone morphogenetic protein (BMP) antagonist. We show here that SOST/sclerostin is expressed exclusively by osteocytes in mouse and human bone and inhibits the differentiation and mineralization of murine preosteoblastic cells (KS483). Although sclerostin shares some of the actions of the BMP antagonist noggin, we show here that it also has actions distinctly different from it. In contrast to noggin, sclerostin did not inhibit basal alkaline phosphatase (ALP) activity in KS483 cells, nor did it antagonize BMP-stimulated ALP activity in mouse C2C12 cells. In addition, sclerostin had no effect on BMP-stimulated Smad phosphorylation and direct transcriptional activation of MSX-2 and BMP response element reporter constructs in KS483 cells. Its unique localization and action on osteoblasts suggest that sclerostin may be the previously proposed osteocyte-derived factor that is transported to osteoblasts at the bone surface and inhibits bone formation.
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影响因子：
11.4
作者：
Goumans, MJ;Valdimarsdottir, G;ten Dijke, P
通讯作者：
ten Dijke, P
影响因子：
4
作者：
BEIGHTON, P
通讯作者：
BEIGHTON, P
影响因子：
4
作者：
Balemans, W;Patel, N;Van Hul, W
通讯作者：
Van Hul, W
影响因子：
4.1
作者：
Haaijman, A;Karperien, M;Burger, EH
通讯作者：
Burger, EH
影响因子：
6.2
作者：
Dang, ZC;Van Bezooijen, RL;Löwik, CWGM
通讯作者：
Löwik, CWGM