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Innervation by the sSensory nervous system innervation plays a key role inis important for skeletal development and in orchestration of bone remodeling and regeneration. However, it is unclear how and in which bone cells can sensory nerves nerves act to for controlregulating these processes remains unclear. HereIn this study, we presentshow a microfluidic coculture system involving comprising dorsal root ganglion (DRG) neurons and mesenchymal stem cells (MSCs), which that more faithfully represents the in vivo situation scenario of bone sensory innervation more appropriately. We report that DRG neurons promote the osteogenic differentiation capacity of MSCs, by mediating the increase increasing of alkaline phosphatase activity and the upregulation ofng osteoblast-specific genesgene expression. Furthermore, we show that Further, DRG neurons have a positively impact on Cx43 levels in MSCs during osteoblastogenesis, especially particularly at at an early stage of this process. Conversely, we described aDRG neurons negatively impact of DRG neurons on MSCs N-cadherin expression in MSCs at a later stage of the process. Finally, we demonstrate a the cytoplasmic accumulation and nuclearof translocation of β-catenin translocation 1 into the nucleus, and the subsequently lLymphoid Eenhancer - Bbinding  2 Ffactor 1-responsive transcriptional activation of downstream genes in cocultured MSCs. Together, oOur study provides stronga robust body of  3 evidence that the osteoblast differentiation potential of MSCs is enhanced the direct interaction ofwhen DRG neurons directly interact 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 theby regulation of Cx43 and N-cadherin expression and activation of the canonical/β-catenin Wnt signaling pathway.

Explanations

Innervation by from the sensory nervous system plays a key role inis important for skeletal development and in orchestration of bone remodeling and regeneration. However, it is unclear how and in which bone cells can sensory nerves nerves act to control these processes remains unclear. Here, we presentshow a microfluidic coculture system comprising dorsal root ganglion (DRG) neurons and mesenchymal stem cells (MSCs), which that more faithfully represents the in vivo scenario of bone sensory innervation more appropriately. We report that DRG neurons promote the osteogenic differentiation capacity of MSCs, by mediating an the increase in of alkaline phosphatase activity and the upregulation ofng osteoblast-specific genes. Furthermore, we show that DRG neurons have a positively impact on Cx43 levels in MSCs during osteoblastogenesis, especially particularly at at an early stage of this process. Conversely, we described a negative impact of DRG neurons on MSCs N-cadherin expression in MSCs at a later stage of the process. Finally, we demonstrate a the cytoplasmic accumulation of β-catenin and translocation of β-catenin  1 into the nucleus, and the subsequently lLymphoid Eenhancer- Bbinding  2 Ffactor 1  3 -responsive transcriptional activation of downstream genes in cocultured MSCs. Together, oOur study provides strong a robust body of evidence that the direct interaction of DRG neurons with MSCs in a bone-like microenvironment leads to an enhancement ofenhances the 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.

Explanations

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