Effect of RANKL inhibition on fibrous dysplasia lesions (mouse). Effect of RANKL inhibition on fibrous dysplasia lesions (mouse)

we investigated mechanisms underlying RANKL inhibition with the monoclonal antibody denosumab on FD tissue, and its likely indirect effects on osteoprogenitors, by evaluating human FD tissue pre and post-treatment and in murine in vivo pre-clinical models. Results from this study demonstrate that, beyond its expected anti-osteoclastic effects, denosumab reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic maturation, leading to increased bone formation within lesions Overall design: For human analysis :6 pairs of human samples (FD patients) before and after denosumab treatment. For Mouse model: 6 uninduced mice (WT), 5 mice induced for FD and treated with Isotype control and 6 mice induced for FD and treated with αRANKL antibody

本研究通过评估经地诺单抗（denosumab）治疗前后的人纤维结构不良（fibrous dysplasia, FD）组织样本，结合小鼠体内临床前模型，探究单克隆抗体地诺单抗对FD组织的核因子κB受体活化因子配体（Receptor Activator of Nuclear Factor κB Ligand, RANKL）的抑制机制，及其对骨祖细胞的潜在间接效应。本研究结果表明，地诺单抗除具备预期的抗破骨细胞活性作用外，还可通过降低FD病灶内细胞增殖、促进成骨成熟，抑制FD病灶活性，最终提升病灶内骨形成水平。
实验整体设计如下：
1. 人体样本分析：纳入6对FD患者经地诺单抗治疗前后的人体组织样本；
2. 小鼠模型实验：设置3组小鼠，分别为6只未诱导的野生型（Wild Type, WT）小鼠、5只诱导构建FD模型并给予同型对照抗体处理的小鼠，以及6只诱导构建FD模型并给予抗RANKL抗体处理的小鼠。