Born-Evers Gabriella, Orr Ashley L, Hulsey Elizabeth Q, Squire Maria E, Hum Julia M, Plotkin Lilian, Sampson Catherine, Hommel Jonathan, Lowery Jonathan W
Division of Biomedical Science, College of Osteopathic Medicine, Marian University, 3200 Cold Spring Rd, Indianapolis, IN 46222, USA.
Bone & Muscle Research Group, Marian University, Indianapolis, IN 46222, USA.
Life (Basel). 2023 Mar 31;13(4):918. doi: 10.3390/life13040918.
Global loss of the neuropeptide Neuromedin-U (NMU) is associated with increased bone formation and high bone mass in male and female mice by twelve weeks of age, suggesting that NMU suppresses osteoblast differentiation and/or activity in vivo. NMU is highly expressed in numerous anatomical locations including the skeleton and the hypothalamus. This raises the possibility that NMU exerts indirect effects on bone remodeling from an extra-skeletal location such as the brain. Thus, in the present study we used microinjection to deliver viruses carrying short-hairpin RNA designed to knockdown expression in the hypothalamus of 8-week-old male rats and evaluated the effects on bone mass in the peripheral skeleton. Quantitative RT-PCR confirmed approximately 92% knockdown of in the hypothalamus. However, after six weeks, micro computed tomography on tibiae from -knockdown rats demonstrated no significant change in trabecular or cortical bone mass as compared to controls. These findings are corroborated by histomorphometric analyses which indicate no differences in osteoblast or osteoclast parameters between controls and -knockdown samples. Collectively, these data suggest that hypothalamus-derived NMU does not regulate bone remodeling in the postnatal skeleton. Future studies are necessary to delineate the direct versus indirect effects of NMU on bone remodeling.
到12周龄时，神经肽神经介素U（NMU）在雌雄小鼠体内的整体缺失与骨形成增加和骨量增加有关，这表明NMU在体内抑制成骨细胞分化和/或活性。NMU在包括骨骼和下丘脑在内的许多解剖位置高度表达。这增加了NMU从诸如大脑等骨骼外位置对骨重塑产生间接影响的可能性。因此，在本研究中，我们使用显微注射法将携带短发夹RNA的病毒注入8周龄雄性大鼠的下丘脑，以敲低其表达，并评估对周围骨骼骨量的影响。定量逆转录聚合酶链反应（qRT-PCR）证实下丘脑内的表达被敲低了约92%。然而，六周后，对NMU敲低大鼠胫骨进行的显微计算机断层扫描显示，与对照组相比，小梁骨或皮质骨量没有显著变化。组织形态计量学分析证实了这些发现，该分析表明对照组和NMU敲低样本之间的成骨细胞或破骨细胞参数没有差异。总体而言，这些数据表明，下丘脑来源的NMU不调节出生后骨骼的骨重塑。未来有必要开展研究来阐明NMU对骨重塑的直接和间接影响。
