Osteoprotegerin (OPG) inhibits the ability of receptor activator of nuclear factor κB (NF-κB) 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.

骨保护素（OPG）抑制核因子κB（NF-κB）配体（RANKL）的受体激活剂刺激骨吸收破骨细胞的分化，活性和存活。小鼠的遗传研究表明，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Tnfrsf11b的条件删除，从不同的细胞群体中编码OPG，以识别小鼠中OPG的功能相关来源。通常认为可以提供OPG的两种细胞类型B淋巴细胞和骨细胞的缺失对骨量几乎没有影响。相比之下，删除Tnfrsf11b成骨细胞中的成骨细胞增加骨吸收并减少骨量，其程度类似于种系缺失，表明成骨细胞是OPG的重要来源。这些结果表明，除产生新的骨基质外，成骨细胞还通过抑制RANKL活性而在终止骨重塑周期的吸收阶段中发挥积极作用。