Division of Biomedical Science, Marian University College of Osteopathic Medicine, Indianapolis, IN, USA; Bone & Mineral Research Group, Marian University, Indianapolis, IN, USA.
Department of Biology, The University of Scranton, Scranton, PA, USA.
Biochem Biophys Res Commun. 2020 Apr 16;524(4):890-894. doi: 10.1016/j.bbrc.2020.02.003. Epub 2020 Feb 11.
Osteoporosis is a disease of low bone mass that places individuals at enhanced risk for fracture, disability, and death. Osteoporosis rates are expected to rise significantly in the coming decades yet there are limited pharmacological treatment options, particularly for long-term management of this chronic condition. The drug development pipeline is relatively bereft of new strategies, causing an urgent and unmet need for developing new strategies and targets for treating osteoporosis. Here, we examine a lesser-studied bone remodeling pathway, Neuromedin U (NMU), which is expressed in the bone microenvironment along with its cognate receptors NMU receptor 1 (NMUR1) and 2 (NMUR2). We independently corroborate a prior report that global loss of NMU expression leads to high bone mass and test the hypothesis that NMU negatively regulates osteoblast differentiation. Consistent with this, in vitro studies reveal NMU represses osteoblastic differentiation of osteogenic precursors but, in contrast, promotes osteoblastic marker expression, proliferation and activity of osteoblast-like cells. Phospho-profiling arrays were used to detail differential signaling outcomes that may underlie the opposite responses of these cell types. Collectively, our findings indicate that NMU exerts cell-type-specific responses to regulate osteoblast differentiation and activity.
骨质疏松症是一种低骨量疾病，使个体面临更高的骨折、残疾和死亡风险。预计未来几十年骨质疏松症的发病率将显著上升，但治疗这种慢性疾病的药物选择有限，特别是长期治疗。药物研发管道相对缺乏新策略，因此迫切需要开发治疗骨质疏松症的新策略和靶点。在这里，我们研究了一个研究较少的骨重塑途径，即神经肽 U（NMU），它与同源受体 NMU 受体 1（NMUR1）和 2（NMUR2）一起在骨微环境中表达。我们独立证实了之前的一份报告，即 NMU 的全局缺失表达导致高骨量，并检验了 NMU 负向调节成骨细胞分化的假设。与这一假设一致的是，体外研究表明 NMU 抑制成骨前体细胞的成骨细胞分化，但相反，促进成骨样细胞的成骨细胞标志物表达、增殖和活性。磷酸化谱分析用于详细描述可能解释这些细胞类型相反反应的差异信号转导结果。总的来说，我们的研究结果表明，NMU 对成骨细胞分化和活性具有细胞类型特异性的反应。
