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細胞生物学のアドバンス校正サンプル
感覚神経系からの神経支配は、骨格の発生および骨の再形成や再生の調整に重要となる。しかし、感覚神経がどのように、どの骨細胞に作用し、これらのプロセスを制御しているのかについては、未だ不明である。我々は、後根神経節（DRG）ニューロンおよび間葉系幹細胞（MSCs）からなるマイクロ流体共培養系を用いて、生体内での骨感覚神経支配の概要をより適切に表現することに成功した。DRGニューロンは、アルカリホスファターゼ活性の上昇や骨芽細胞特異的遺伝子の発現増加を介し、MSCの骨形成分化能を促進することを報告する。さらに、DRGニューロンは、骨芽細胞形成中、特にその初期段階においてMSC内のCx43濃度に有用な影響を与えることを示す。それとは逆に、DRGニューロンが、骨芽細胞形成の後期においてN-カドヘリンの発現に負の影響を与えることも述べる。最後に、共培養MSCにおけるβ-カテニンの細胞質への蓄積と核への移行、およびそれに続くリンパ系エンハンサー結合因子1応答性の下流遺伝子の転写活性化について説明する。本研究は、骨類似の微小環境におけるDRGニューロンとMSCsの直接的な相互作用が、MSCsの骨芽細胞分化能を高めるという強力な証拠を提示するものである。DRGニューロンのMSCsに対する骨形成作用は、Cx43およびN-カドヘリンの発現調節および標準的／β-カテニンWntシグナル伝達経路の活性化を介して行われる。
Innervation by the sensory nervous system plays a key role in skeletal development and in orchestration of bone remodeling and regeneration. However, it is unclear how and in which bone cells can sensory nerves act to control these processes. Here, we show a microfluidic coculture system comprising dorsal root ganglion (DRG) neurons and mesenchymal stem cells (MSCs) that more faithfully represents the in vivo scenario of bone sensory innervation. We report that DRG neurons promote the osteogenic differentiation capacity of MSCs, by mediating the increase of alkaline phosphatase activity and the upregulation of osteoblast-specific genes. Furthermore, we show that DRG neurons have a positive impact on Cx43 levels in MSCs during osteoblastogenesis, especially at an early stage of this process. Conversely, we described a negative impact of DRG neurons on MSCs N-cadherin expression at a later stage. Finally, we demonstrate a cytoplasmic accumulation of β-catenin translocation into the nucleus, and subsequently Lymphoid Enhancer Binding Factor 1—responsive transcriptional activation of downstream genes in cocultured MSCs. Together, our study provides a robust body of evidence that the direct interaction of DRG neurons with MSCs in a bone-like microenvironment leads to an enhancement of osteoblast differentiation potential of MSCs. The osteogenic effect of DRG neurons on MSCs is mediated through the regulation of Cx43 and N-cadherin expression and activation of the canonical/β-catenin Wnt signaling pathway.
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- The sentence has been restructured to improve clarity and readability.
- As per the context, the authors are referring to an internal cell system. Accordingly the word "show" is inappropriate in this context and thus has been revised to "present."
- A technical edit has been at this instance to enhance the technical accuracy of the file. Technically, "upregulation of gene" is incorrect as it is always referred to as "upregulation of gene expression."
- Here, the sentence has been revised to clearly indicate that accumulation and translocation ofβ-catenin are being referred to.
- A compound modifier contains 2 or more words, which act together as one adjective and are connected by hyphens. Hyphens are used with these terms so that their meaning is understood clearly.
- The text alongside has been revised to convey the intended meaning in a more concise manner.
- Incorrect preposition error has been rectified. Here, the use of "through" is incorrect as it implies "an continuing action" in this case. Therefore "by" is a correct preposition.
Sensory nervous system innervation is important for skeletal development and orchestration of bone remodeling and regeneration. However, how and in which bone cells sensory nerves act for regulating these processes remains unclear. In this study, we present a microfluidic coculture system involving dorsal root ganglion (DRG) neurons and mesenchymal stem cells (MSCs), which represents the in vivo situation of bone sensory innervation more appropriately. We report that DRG neurons promote the osteogenic differentiation capacity of MSCs by increasing alkaline phosphatase activity and upregulating osteoblast-specific gene expression. Further, DRG neurons positively impact Cx43 levels in MSCs during osteoblastogenesis, particularly at an early stage of this process. Conversely, DRG neurons negatively impact N-cadherin expression in MSCs at a later stage of the process. Finally, we demonstrate the cytoplasmic accumulation and nuclear translocation of β-catenin and the subsequent lymphoid enhancer-binding factor 1-responsive transcriptional activation of downstream genes in cocultured MSCs. Our study provides strong evidence that the osteoblast differentiation potential of MSCs is enhanced when DRG neurons directly interact with MSCs in a bone-like microenvironment. The osteogenic effect of DRG neurons on MSCs is mediated by regulation of Cx43 and N-cadherin expression and activation of the canonical/β-catenin Wnt signaling pathway.
