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Cellular mechanisms of bone remodeling

机译：骨骼重塑的细胞机制

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Bone remodeling is a tightly regulated process securing repair of microdamage (targeted remodeling) and replacement of old bone with new bone through sequential osteoclastic resorption and osteoblastic bone formation. The rate of remodeling is regulated by a wide variety of calcitropic hormones (PTH, thyroid hormone, sex steroids etc.). In recent years we have come to appreciate that bone remodeling proceeds in a specialized vascular structure,—the Bone Remodeling Compartment (BRC). The outer lining of this compartment is made up of flattened cells, displaying all the characteristics of lining cells in bone including expression of OPG and RANKL. Reduced bone turnover leads to a decrease in the number of BRCs, while increased turnover causes an increase in the number of BRCs. The secretion of regulatory factors inside a confined space separated from the bone marrow would facilitate local regulation of the remodeling process without interference from growth factors secreted by blood cells in the marrow space. The BRC also creates an environment where cells inside the structure are exposed to denuded bone, which may enable direct cellular interactions with integrins and other matrix factors known to regulate osteoclast/osteoblast activity. However, the denuded bone surface inside the BRC also constitutes an ideal environment for the seeding of bone metastases, known to have high affinity for bone matrix. Circulating osteoclast- and osteoblast precursor cells have been demonstrated in peripheral blood. The dominant pathway regulating osteoclast recruitment is the RANKL/OPG system, while many different factors (RUNX, Osterix) are involved in osteoblast differentiation. Both pathways are modulated by calcitropic hormones.
机译：骨重塑是严格控制的过程，可通过顺序的破骨细胞吸收和成骨细胞形成来确保微损伤的修复（针对性重塑）和新骨替代旧骨。重塑的速率受多种促钙激素（PTH，甲状腺激素，性类固醇等）调节。近年来，我们逐渐意识到，骨骼重塑是在一种特殊的血管结构中进行的，即骨重塑室（BRC）。该隔室的外衬由扁平细胞组成，显示了骨中衬细胞的所有特征，包括OPG和RANKL的表达。骨转换的减少导致BRC数量的减少，而转换的增加导致BRC数量的增加。与骨髓分开的狭窄空间内调节因子的分泌将促进重塑过程的局部调节，而不会受到骨髓腔中血细胞分泌的生长因子的干扰。 BRC还创建了一个结构内部细胞暴露于裸露骨的环境，这可能使细胞与整联蛋白和其他已知的调节破骨细胞/成骨细胞活性的基质因子直接相互作用。但是，BRC内部裸露的骨表面也为播种骨转移瘤构成了理想的环境，已知该转移灶对骨基质具有很高的亲和力。在外周血中已经证明循环的破骨细胞和成骨细胞前体细胞。调控破骨细胞募集的主要途径是RANKL / OPG系统，而成骨细胞分化涉及许多不同的因素（RUNX，Osterix）。两种途径均受促钙激素调节。

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