Center for Musculoskeletal Disease Research, University of Arkansas for Medical Sciences, Little Rock, 72205, AR, USA.
Department of Orthopaedic Surgery, University of Arkansas for Medical Sciences, Little Rock, 72205, AR, USA.
Nat Commun. 2018 Jul 25;9(1):2909. doi: 10.1038/s41467-018-05244-y.
Receptor activator of NFkB ligand (RANKL) is a TNF-family cytokine required for osteoclast formation, as well as immune cell and mammary gland development. It is produced as a membrane-bound protein that can be shed to form a soluble protein. We created mice harboring a sheddase-resistant form of RANKL, in which soluble RANKL is undetectable in the circulation. Lack of soluble RANKL does not affect bone mass or structure in growing mice but reduces osteoclast number and increases cancellous bone mass in adult mice. Nonetheless, the bone loss caused by estrogen deficiency is unaffected by the lack of soluble RANKL. Lymphocyte number, lymph node development, and mammary gland development are also unaffected by the absence of soluble RANKL. These results demonstrate that the membrane-bound form of RANKL is sufficient for most functions of this protein but that the soluble form does contribute to physiological bone remodeling in adult mice.
核因子 κB 受体激活物配体（RANKL）是一种 TNF 家族细胞因子，对于破骨细胞的形成以及免疫细胞和乳腺的发育是必需的。它作为一种膜结合蛋白被产生，这种膜结合蛋白可以被脱落形成一种可溶性蛋白。我们构建了一种带有破骨细胞溶解酶抗性形式的 RANKL 的小鼠，其中循环中检测不到可溶性 RANKL。可溶性 RANKL 的缺乏并不影响生长中的小鼠的骨量或结构，但减少了成年小鼠的破骨细胞数量并增加了小梁骨量。尽管如此，雌激素缺乏引起的骨丢失不受可溶性 RANKL 的缺乏影响。淋巴细胞数量、淋巴结发育和乳腺发育也不受可溶性 RANKL 缺乏的影响。这些结果表明，RANKL 的膜结合形式足以发挥该蛋白的大多数功能，但可溶性形式确实有助于成年小鼠的生理性骨重塑。
