Local Production of Osteoprotegerin by Osteoblasts Suppresses Bone Resorption
Local Production of Osteoprotegerin by Osteoblasts Suppresses Bone Resorption
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DOI：
10.1016/j.celrep.2020.108052
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发表时间：
2020-09-08
期刊：
影响因子：
8.8
通讯作者：
O'Brien, Charles A.
中科院分区：
文献类型：
--
作者：
Cawley, Keisha M.;Bustamante-Gomez, Nancy Cecile;O'Brien, Charles A.
骨保护素 (OPG) 抑制核因子 kappa B (NF-kappa B) 配体 (RANKL) 受体激活剂刺激破骨细胞分化、活性和存活的能力。小鼠遗传学研究表明，骨细胞是 RANKL 的重要来源，但 OPG 的细胞来源尚不清楚。我们使用来自不同细胞群的编码 OPG 的 Tnfrsf11b 的条件删除来鉴定小鼠中功能相关的 OPG 来源。 B 淋巴细胞和骨细胞（通常被认为提供 OPG 的两种细胞类型）的缺失对骨量影响很小或没有影响。相比之下，从成骨细胞中删除 Tnfrsf11b 会增加骨吸收并减少骨量，其程度与种系删除类似，表明成骨细胞是 OPG 的重要来源。这些结果表明，除了产生新的骨基质外，成骨细胞还通过抑制 RANKL 活性在终止骨重塑周期的吸收阶段中发挥积极作用。
Osteoprotegerin (OPG) inhibits the ability of receptor activator of nuclear factor kappa B (NF-kappa B) ligand (RANKL) to stimulate the differentiation, activity, and survival of bone-resorbing osteoclasts. Genetic studies in mice show that osteocytes are an important source of RANKL, but the cellular sources of OPG are unclear. We use conditional deletion of Tnfrsf11b, which encodes OPG, from different cell populations to identify functionally relevant sources of OPG in mice. Deletion from B lymphocytes and osteocytes, two cell types commonly thought to supply OPG, has little or no impact on bone mass. By contrast, deletion of Tnfrsf11b from osteoblasts increases bone resorption and reduces bone mass to an extent similar to germline deletion, demonstrating that osteoblasts are an essential source of OPG. These results suggest that, in addition to producing new bone matrix, osteoblasts also play an active role in terminating the resorption phase of the bone remodeling cycle by suppressing RANKL activity.