We previously described a new osteogenic growth factor, osteolectin/Clec11a, which is required for the maintenance of skeletal bone mass during adulthood. Osteolectin binds to Integrin α11 (Itga11), promoting Wnt pathway activation and osteogenic differentiation by leptin receptor⁺ (LepR⁺) stromal cells in the bone marrow. Parathyroid hormone (PTH) and sclerostin inhibitor (SOSTi) are bone anabolic agents that are administered to patients with osteoporosis. Here we tested whether osteolectin mediates the effects of PTH or SOSTi on bone formation. We discovered that PTH promoted Osteolectin expression by bone marrow stromal cells within hours of administration and that PTH treatment increased serum osteolectin levels in mice and humans. Osteolectin deficiency in mice attenuated Wnt pathway activation by PTH in bone marrow stromal cells and reduced the osteogenic response to PTH in vitro and in vivo. In contrast, SOSTi did not affect serum osteolectin levels and osteolectin was not required for SOSTi-induced bone formation. Combined administration of osteolectin and PTH, but not osteolectin and SOSTi, additively increased bone volume. PTH thus promotes osteolectin expression and osteolectin mediates part of the effect of PTH on bone formation.

我们之前描述了一种新的成骨生长因子，骨凝集素/Clec11a，它是成年期维持骨骼骨量所必需的。骨凝集素与整合素 α11 (Itga11) 结合，促进 Wnt 通路激活和骨髓中瘦素受体⁺ (LepR ⁺ ) 基质细胞的成骨分化。甲状旁腺激素 (PTH) 和硬化素抑制剂 (SOSTi) 是用于骨质疏松症患者的骨合成代谢剂。在这里，我们测试了骨凝集素是否介导 PTH 或 SOSTi 对骨形成的影响。我们发现 PTH在给药数小时内促进骨髓基质细胞的骨凝集素表达，并且 PTH 治疗增加了小鼠和人类的血清骨凝集素水平。小鼠骨凝集素缺乏减弱了骨髓基质细胞中 PTH 对 Wnt 通路的激活，并降低了体外和体内对 PTH 的成骨反应。相反，SOSTi 不影响血清骨凝集素水平，并且 SOSTi 诱导的骨形成不需要骨凝集素。骨凝集素和 PTH 的联合给药，而不是骨凝集素和 SOSTi 的联合给药，可额外增加骨量。因此，PTH 促进骨凝集素表达，骨凝集素介导 PTH 对骨形成的部分影响。