美国加州大学Holly A. Ingraham和Thomas H. Ambrosi共同合作，近期取得重要工作进展。他们研究发现了一种能增强骨骼生成的母体脑激素。相关研究成果2024年7月10日在线发表于《自然》杂志上。

据介绍，在哺乳期母亲中，产奶对钙（Ca²⁺）的高需求会引发严重的骨质流失。尽管雌激素通常通过促进骨形成来抵消过度的骨吸收，但这种性类固醇在产后期间会急剧下降。

研究人员发现，从弓状核（ARC^KISS1）的KISS1神经元分泌的脑源性细胞通讯网络因子3（CCN3）填补了这一空白，并作为一种强效的骨合成代谢因子，在哺乳期雌性体内构建骨骼。研究人员之前报道的女性特异性致密骨表型起源于一种体液因子，该因子促进骨量并作用于骨骼干细胞，以增加其频率和骨软骨生成潜力。

这种循环因子被鉴定为CCN3，这是一种来自ARC^KISS1神经元的脑源性激素，能够刺激小鼠和人类骨骼干细胞的活性，增加骨重塑，加速年轻和老年小鼠的骨折修复。在哺乳期间检测到ARC^KISS1神经元中CCN3的表达爆发揭示了CCN3在正常女性生理中的作用。在减少ARC^KISS1神经元中的CCN3后，哺乳期母亲失去了骨骼，在低钙饮食的挑战下无法维持后代。

总之，这一研究结果确定CCN3作为一种潜在的新型治疗性骨合成代谢激素，适用于男性和女性，同时也定义了一种新的母体脑激素，以确保哺乳动物的物种生存。

附：英文原文

Title: A maternal brain hormone that builds bone

Author: Babey, Muriel E., Krause, William C., Chen, Kun, Herber, Candice B., Torok, Zsofia, Nikkanen, Joni, Rodriguez, Ruben, Zhang, Xiao, Castro-Navarro, Fernanda, Wang, Yuting, Wheeler, Erika E., Villeda, Saul, Leach, J. Kent, Lane, Nancy E., Scheller, Erica L., Chan, Charles K. F., Ambrosi, Thomas H., Ingraham, Holly A.

Issue&Volume: 2024-07-10

Abstract: In lactating mothers, the high calcium (Ca2+) demand for milk production triggers significant bone loss1. Although oestrogen normally counteracts excessive bone resorption by promoting bone formation, this sex steroid drops precipitously during this postpartum period. Here we report that brain-derived cellular communication network factor3 (CCN3) secreted from KISS1 neurons of the arcuate nucleus (ARCKISS1) fills this void and functions as a potent osteoanabolic factor to build bone in lactating females. We began by showing that our previously reported female-specific, dense bone phenotype2 originates from a humoral factor that promotes bone mass and acts on skeletal stem cells to increase their frequency and osteochondrogenic potential. This circulatory factor was then identified as CCN3, a brain-derived hormone from ARCKISS1 neurons that is able to stimulate mouse and human skeletal stem cell activity, increase bone remodelling and accelerate fracture repair in young and old mice of both sexes. The role of CCN3 in normal female physiology was revealed after detecting a burst of CCN3 expression in ARCKISS1 neurons coincident with lactation. After reducing CCN3 in ARCKISS1 neurons, lactating mothers lost bone and failed to sustain their progeny when challenged with a low-calcium diet. Our findings establish CCN3 as a potentially new therapeutic osteoanabolic hormone for both sexes and define a new maternal brain hormone for ensuring species survival in mammals.

DOI: 10.1038/s41586-024-07634-3

Source: https://www.nature.com/articles/s41586-024-07634-3