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首页> 外文期刊>The journal of clinical investigation >Osteoclast-secreted CTHRC1 in the coupling of bone resorption to formation
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Osteoclast-secreted CTHRC1 in the coupling of bone resorption to formation

机译：破骨细胞分泌的CTHRC1在骨吸收与形成的耦合中

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Bone remodeling is characterized by the sequential, local tethering of osteoclasts and osteoblasts and is key to the maintenance of bone integrity. While bone matrix–mobilized growth factors, such as TGF-β, are proposed to regulate remodeling, no in vivo evidence exists that an osteoclast-produced molecule serves as a coupling factor for bone resorption to formation. We found that CTHRC1, a protein secreted by mature bone-resorbing osteoclasts, targets stromal cells to stimulate osteogenesis. Cthrc1 expression was robustly induced when mature osteoclasts were placed on dentin or hydroxyapatite, and also by increasing extracellular calcium. Cthrc1 expression in bone increased in a high-turnover state (such as that induced by RANKL injections in vivo), but decreased in conditions associated with suppressed bone turnover (such as with aging and after alendronate treatment). Targeted deletion of Cthrc1 in mice eliminated Cthrc1 expression in bone, whereas its deficiency in osteoblasts did not exert any significant effect. Osteoclast-specific deletion of Cthrc1 resulted in osteopenia due to reduced bone formation and impaired the coupling process after resorption induced by RANKL injections, impairing bone mass recovery. These data demonstrate that CTHRC1 is an osteoclast-secreted coupling factor that regulates bone remodeling.
机译：骨重塑的特征是破骨细胞和成骨细胞的顺序局部束缚，并且是维持骨完整性的关键。虽然提出了通过骨基质移动的生长因子（例如TGF-β）来调节重塑，但没有体内证据表明破骨细胞产生的分子充当骨吸收形成的耦合因子。我们发现CTHRC1是成熟的骨吸收破骨细胞分泌的蛋白质，其靶向基质细胞来刺激成骨。当成熟的破骨细胞置于牙本质或羟基磷灰石上时，还可以通过增加细胞外钙来强烈诱导Cthrc1表达。骨中的Cthrc1表达在高周转状态下增加（例如由体内RANKL注射诱导），但在与骨转换受抑制有关的条件下（例如衰老和阿仑膦酸盐治疗后）降低。小鼠中Cthrc1的靶向缺失消除了骨中Cthrc1的表达，而其在成骨细胞中的缺乏没有发挥任何显著作用。 Cthrc1的破骨细胞特异性缺失导致骨质减少，原因是骨形成减少，并在RANKL注射引起的吸收后损害了偶联过程，从而损害了骨量的恢复。这些数据表明，CTHRC1是破骨细胞分泌的偶联因子，可调节骨骼重塑。

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