The Sonic Hedgehog signaling pathway regulates inferior alveolar nerve regeneration

Yamada, Yurie; Ohazama, Atsushi; Maeda, Takeyasu; Seo, Kenji

doi:10.1016/j.neulet.2017.12.051

Cited by 26 publications

(35 citation statements)

References 31 publications

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“…The AXONO module was enriched for the Hedgehog signaling pathway and the Estrogen signaling pathway. Sonic hedgehog (Shh) is essential for central nervous system development and is expressed within injured sciatic nerve 56 . Recently, reduced Shh signaling was shown to disturb axon regeneration via misregulated myelin degradation 56 .…”

Section: Discussionmentioning

confidence: 99%

“…Sonic hedgehog (Shh) is essential for central nervous system development and is expressed within injured sciatic nerve 56 . Recently, reduced Shh signaling was shown to disturb axon regeneration via misregulated myelin degradation 56 . Estrogen signaling has also been implicated in axon regeneration by accelerating peripheral nerve regeneration and increasing motoneuron participation 57,58 .…”

Section: Discussionmentioning

confidence: 99%

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A network biology approach to unraveling inherited axonopathies

Bis-Brewer

Danzi

Wuchty

et al. 2019

Sci Rep

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Inherited axonopathies represent a spectrum of disorders unified by the common pathological mechanism of length-dependent axonal degeneration. Progressive axonal degeneration can lead to both Charcot-Marie-Tooth type 2 (CMT2) and Hereditary Spastic Paraplegia (HSP) depending on the affected neurons: peripheral motor and sensory nerves or central nervous system axons of the corticospinal tract and dorsal columns, respectively. Inherited axonopathies display an extreme degree of genetic heterogeneity of Mendelian high-penetrance genes. High locus heterogeneity is potentially advantageous to deciphering disease etiology by providing avenues to explore biological pathways in an unbiased fashion. Here, we investigate ‘gene modules’ in inherited axonopathies through a network-based analysis of the Human Integrated Protein-Protein Interaction rEference (HIPPIE) database. We demonstrate that CMT2 and HSP disease proteins are significantly more connected than randomly expected. We define these connected disease proteins as ‘proto-modules’ and show the topological relationship of these proto-modules by evaluating their overlap through a shortest-path based measurement. In particular, we observe that the CMT2 and HSP proto-modules significantly overlapped, demonstrating a shared genetic etiology. Comparison of both modules with other diseases revealed an overlapping relationship between HSP and hereditary ataxia and between CMT2 + HSP and hereditary ataxia. We then use the DIseAse Module Detection (DIAMOnD) algorithm to expand the proto-modules into comprehensive disease modules. Analysis of disease modules thus obtained reveals an enrichment of ribosomal proteins and pathways likely central to inherited axonopathy pathogenesis, including protein processing in the endoplasmic reticulum, spliceosome, and mRNA processing. Furthermore, we determine pathways specific to each axonopathy by analyzing the difference of the axonopathy modules. CMT2-specific pathways include glycolysis and gluconeogenesis-related processes, while HSP-specific pathways include processes involved in viral infection response. Unbiased characterization of inherited axonopathy disease modules will provide novel candidate disease genes, improve interpretation of candidate genes identified through patient data, and guide therapy development.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A network biology approach to unraveling inherited axonopathies

Bis-Brewer

Danzi

Wuchty

et al. 2019

Sci Rep

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“…Currently, as advancements and achievements in mesenchymal stem cell (MSC) research are developing rapidly, the use of MSCs to alleviate peripheral nerve injury has drawn researchers’ attention. Studies have reported that both adipose tissue-derived stem cells and bone marrow-derived stem cells are able to differentiate into neural-like cells and finally demonstrate a great inclination to nerve repair and regeneration in vivo [ 5 - 7 ].…”

Section: Introductionmentioning

confidence: 99%

Neurotrophic effects of dental pulp stem cells in repair of peripheral nerve after crush injury

Wang

Pan

et al. 2020

WJSC

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BACKGROUND Nerve diseases and injuries, which are usually accompanied by motor or sensory dysfunction and disorder, impose a heavy burden upon patients and greatly reduce their quality of life. Dental pulp stem cells (DPSCs), derived from the neural crest, have many characteristics that are similar to those of neural cells, indicating that they can be an ideal source for neural repair. AIM To explore the potential roles and molecular mechanisms of DPSCs in crushed nerve recovery. METHODS DPSCs were isolated, cultured, and identified by multilineage differentiation and flow cytometry. Western blot and immunofluorescent staining were applied to analyze the expression levels of neurotrophic proteins in DPSCs after neural induction. Then, we collected the secretions of DPSCs. We analyzed their effects on RSC96 cell proliferation and migration by CCK8 and transwell assays. Finally, we generated a sciatic nerve crush injury model in vivo and used the sciatic function index, walking track analysis, muscle weight, and hematoxylin & eosin (H&E) staining to further evaluate the nerve repair ability of DPSCs. RESULTS DPSCs highly expressed several specific neural markers, including GFAP, S100, Nestin, P75, and NF200, and were inclined toward neural differentiation. Furthermore, neural-induced DPSCs (N-DPSCs) could express neurotrophic factors, including NGF, BDNF, and GDNF. The secretions of N-DPSCs could enhance the proliferation and migration of Schwann cells. In vivo , both DPSC and N-DPSC implants alleviated gastrocnemius muscle atrophy. However, in terms of anatomy and motor function, as shown by H&E staining, immunofluorescent staining, and walking track analyses, the repair effects of N-DPSCs were more sustained, potent, and effective than those of DPSCs and the controls. CONCLUSION In summary, this study demonstrated that DPSCs are inclined to differentiate into neural cells. N-DPSCs express neurotrophic proteins that could enhance the proliferation and migration of SCs. Furthermore, our results suggested that N-DPSCs could help crushed nerves with functional recovery and anatomical repair in vivo . Thus, DPSCs or N-DPSCs could be a promising therapeutic cell source for peripheral nerve repair and regeneration.

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“…5,[91][92][93][94][95] There have been no specific reports illustrating the usage of dental stem cells in IAN injury repair by far. IAN injury mainly happens during mandibular fracture or oral surgery such as the third molar extraction and results in unpleasant complications including dysesthesia, allodynia and hyperalgesia.…”

Section: Inferior Alveolar Nerve Injurymentioning

confidence: 99%

Advances of tooth‐derived stem cells in neural diseases treatments and nerve tissue regeneration

Wang

Tian

et al. 2019

Cell Proliferation

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Nerous system diseases, both central and peripheral, bring an incredible burden onto patients and enormously reduce their quality of life. Currently, there are still no effective treatments to repair nerve lesions that do not have side effects. Stem cellbased therapies, especially those using dental stem cells, bring new hope to neural diseases. Dental stem cells, derived from the neural crest, have many characteristics that are similar to neural cells, indicating that they can be an ideal source of cells for neural regeneration and repair. This review summarizes the neural traits of all the dental cell types, including DPSCs, PDLCs, DFCs, APSCs and their potential applications in nervous system diseases. We have summed up the advantages of dental stem cells in neural repair, such as their neurotrophic and neuroprotective traits, easy harvest and low rejective reaction rate, among others. Taken together, dental stem cells are an ideal cell source for neural tissue regeneration and repair.

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The Sonic Hedgehog signaling pathway regulates inferior alveolar nerve regeneration

Cited by 26 publications

References 31 publications

A network biology approach to unraveling inherited axonopathies

A network biology approach to unraveling inherited axonopathies

Neurotrophic effects of dental pulp stem cells in repair of peripheral nerve after crush injury

Advances of tooth‐derived stem cells in neural diseases treatments and nerve tissue regeneration

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