Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.
University of California San Francisco School of Medicine, San Francisco, California, United States of America.
PLoS One. 2021 Oct 12;16(10):e0250715. doi: 10.1371/journal.pone.0250715. eCollection 2021.
Disuse-induced bone loss is seen following spinal cord injury, prolonged bed rest, and exposure to microgravity. We performed whole transcriptomic profiling of cortical bone using RNA sequencing (RNAseq) and RNA molecular barcoding (NanoString) on a hindlimb unloading (HLU) mouse model to identify genes whose mRNA transcript abundances change in response to disuse. Eleven-week old female C57BL/6 mice were exposed to ambulatory loading or HLU for 7 days (n = 8/group). Total RNA from marrow-flushed femoral cortical bone was analyzed on HiSeq and NanoString platforms. The expression of several previously reported genes associated with Wnt signaling and metabolism was altered by HLU. Furthermore, the increased abundance of transcripts, such as Pfkfb3 and Mss51, after HLU imply these genes also have roles in the cortical bone's response to altered mechanical loading. Our study demonstrates that an unbiased approach to assess the whole transcriptomic profile of cortical bone can reveal previously unidentified mechanosensitive genes and may eventually lead to novel targets to prevent disuse-induced osteoporosis.
废用性骨丢失可见于脊髓损伤、长时间卧床和暴露于微重力环境中。我们使用 RNA 测序（RNAseq）和 RNA 分子条码（NanoString）对后肢去负荷（HLU）小鼠模型进行了皮质骨的全转录组谱分析，以确定那些其 mRNA 转录丰度因废用而发生变化的基因。11 周龄雌性 C57BL/6 小鼠接受了 7 天的步行负荷或 HLU（每组 n=8）。对来自骨髓冲洗股骨皮质骨的总 RNA 进行了 HiSeq 和 NanoString 平台分析。HLU 改变了几个先前报道的与 Wnt 信号和代谢相关的基因的表达。此外，HLU 后 Pfkfb3 和 Mss51 等转录本丰度的增加表明这些基因在皮质骨对机械负荷改变的反应中也有作用。我们的研究表明，采用无偏方法评估皮质骨的全转录组谱可以揭示以前未识别的机械敏感基因，并最终可能为预防废用性骨质疏松症提供新的靶点。
