Nell-1 promotes the neural-like differentiation of dental pulp cells

Han, Qi; Wei, Qiang; Wu, Jiameng; Li, Mengyue; Fang, Yixuan; Zhu, Haobo; Wang, Xiaoying

doi:10.1016/j.bbrc.2019.04.028

Cited by 10 publications

(8 citation statements)

References 31 publications

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“…tooth innervation occurs through vasculogenesis (Shadad et al, 2019). In this study, we found that Nell-1 can enhance the expression of proteins and angiogenetic genes as early as day 2, which was almost the same rate as that of the odontoblastic and neural-like differentiation of DPSCs (Liu et al, 2016;Han et al, 2019). Subsequent experiments will be conducted to confirm the relevant mechanisms.…”

Section: Discussionmentioning

confidence: 57%

“…Subsequent experiments will be conducted to confirm the relevant mechanisms. Nell-1 application may be a promising strategy in dental pulp regeneration field since its contribution to dentin formation, neurogenesis and angiogenesis (Liu et al, 2016;Han et al, 2019). Xuan et al (2018) confirmed that human deciduous autologous tooth stem cells can regenerate the whole dental pulp and have a promising effect on pulp regeneration; however, the mechanisms are still unclear.…”

Section: Discussionmentioning

confidence: 91%

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Novel Molecule Nell-1 Promotes the Angiogenic Differentiation of Dental Pulp Stem Cells

Wang

Han

et al. 2021

Front. Physiol.

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IntroductionThis work aimed to reveal the crucial role of Nell-1 in the angiogenic differentiation of human dental pulp stem cells (DPSCs) alone or co-cultured with human umbilical vein endothelial cell (HUVECs) in vitro and whether this molecule is involved in the pulp exposure model in vivo.MethodsImmunofluorescence was conducted to ascertain the location of Nell-1 on DPSCs, HUVECs, and normal rat dental tissues. RT-PCR, Western blot, and ELISA were performed to observe the expression levels of angiogenic markers and determine the angiogenic differentiation of Nell-1 on DPSCs alone or co-cultured with HUVECs, as well as in vitro tube formation assay. Blood vessel number for all groups was observed and compared using immunohistochemistry by establishing a rat pulp exposure model.ResultsNell-1 is highly expressed in the nucleus of DPSCs and HUVECs and is co-expressed with angiogenic markers in normal rat pulp tissues. Hence, Nell-1 can promote the angiogenic marker expression in DPSCs alone and co-cultured with other cells and can enhance angiogenesis in vitro as well as in the pulp exposure model.ConclusionNell-1 may play a positive role in the angiogenic differentiation of DPSCs.

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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 91%

Novel Molecule Nell-1 Promotes the Angiogenic Differentiation of Dental Pulp Stem Cells

Wang

Han

et al. 2021

Front. Physiol.

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“…The exposed rat pulps capped with Nell-1 plus BMP-2 had superior ability in inducing reparative dentin formation with dentin tubules and in reducing the inflammatory cell response as compared with BMP-2 alone (Wu et al 2019). Additionally, Nell-1 promoted neural marker expression in rat dental pulp tissues when the tissues were exposed to an inflammatory environment (Han et al 2019). Thus, aside from effects on the craniofacial skeleton, Nell-1 has crucial functions to the tooth and periodontal tissues.…”

Section: Novel Functional Properties Of Nell-1 In Tissues Beyond Bonementioning

confidence: 99%

“…In well-developed teeth, Nell-1 was mainly expressed in the body and process of odontoblasts and endothelial cells of the blood vessels (Tang et al 2013). In vitro, Nell-1 promoted the osteogenic differentiation of human periodontal ligament stem cells (Chen et al 2012) and the odontoblastic differentiation of human dental pulp cells (Han et al 2019). In vivo, besides the aforementioned alveolar bone defect repair in a rhesus monkey model (Zhang et al 2018), local application of Nell-1 into the buccal mucosa region of the orthodontic tooth accelerated corticotomy-assisted tooth movement in a rat model (Wang et al 2018).…”

Section: Nell-1 In the Oral-dental Systemmentioning

confidence: 99%

Nell-1 Is a Key Functional Modulator in Osteochondrogenesis and Beyond

Zhang

Zheng

et al. 2019

J Dent Res

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Neural EGFL-like 1 (Nell-1) is a well-studied osteogenic factor that has comparable osteogenic potency with the Food and Drug Administration–approved bone morphogenic protein 2 (BMP-2). In this review, which aims to summarize the advanced Nell-1 research in the past 10 y, we start with the correlation of structural and functional relevance of the Nell-1 protein with the identification of a specific receptor of Nell-1, contactin-associated protein-like 4 (Cntnap4), for osteogenesis. The indispensable role of Nell-1 in normal craniofacial and appendicular skeletal development and growth was also defined by using the newly developed tissue-specific Nell-1 knockout mouse lines in addition to the existing transgenic mouse models. With the achievements on Nell-1’s osteogenic therapeutic evaluations from multiple preclinical animal models for local and systemic bone regeneration, the synergistic effect of Nell-1 with BMP-2 on osteogenesis, as well as the advantages of Nell-1 as an osteogenic protein with antiadipogenic, anti-inflammatory, and provascularized characteristics over BMP-2 in bone tissue engineering, is highlighted, which lays the groundwork for the clinical trial approval of Nell-1. At the molecular level, besides the mitogen-activated protein kinase (MAPK) signaling pathway, we emphasize the significant involvement of the Wnt/β-catenin pathway as well as the key regulatory molecules Runt-related transcription factor 2 (Runx2) in Nell-1-induced osteogenesis. In addition, the involvement of Nell-1 in chondrogenesis and its relevant pathologies have been revealed with the participation of the nuclear factor of activated T cells 1 (Nfatc1), Runx3, and Indian hedgehog (Ihh) signaling pathways, although the mechanistic insights of Nell-1’s osteochondrogenic property will be continuously evolving. With this perspective, we elucidate some emerging and novel functional properties of Nell-1 in oral-dental and neural tissues that will be the frontiers of future Nell-1 studies beyond the context of bone and cartilage. As such, the therapeutic potential of Nell-1 continues to evolve and grow with continuous pursuit.

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“…Because many researches demonstrated that hDPSCs have a potential to differentiate toward neurons, hDPSC expected to be used in therapies for neurodegenerative diseases and in fundamental studies of human neural systems [ 32 ]. Expression of neuronal marker proteins has been confirmed in neuronal differentiated hDPSCs [ 26 , 34 ]. Like conventional neurons, they possess functional and active voltage-gated sodium and potassium channels [ 35 , 36 ], and, in some cases, generate action potentials [ 37 ].…”

Section: Introductionmentioning

confidence: 99%

Peripheral-neuron-like properties of differentiated human dental pulp stem cells (hDPSCs)

et al. 2021

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Elucidating the mechanisms underlying human pain sensation requires the establishment of an in vitro model of pain reception comprising human cells expressing pain-sensing receptors and function properly as neurons. Human dental pulp stem cells (hDPSCs) are mesenchymal stem cells and a promising candidate for producing human neuronal cells, however, the functional properties of differentiated hDPSCs have not yet been fully characterized. In this study, we demonstrated neuronal differentiation of hDPSCs via both their expression of neuronal marker proteins and their neuronal function examined using Ca2+ imaging. Moreover, to confirm the ability of nociception, Ca2+ responses in differentiated hDPSCs were compared to those of rat dorsal root ganglion (DRG) neurons. Those cells showed similar responses to glutamate, ATP and agonists of transient receptor potential (TRP) channels. Since TRP channels are implicated in nociception, differentiated hDPSCs provide a useful in vitro model of human peripheral neuron response to stimuli interpreted as pain.

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Nell-1 promotes the neural-like differentiation of dental pulp cells

Cited by 10 publications

References 31 publications

Novel Molecule Nell-1 Promotes the Angiogenic Differentiation of Dental Pulp Stem Cells

Novel Molecule Nell-1 Promotes the Angiogenic Differentiation of Dental Pulp Stem Cells

Nell-1 Is a Key Functional Modulator in Osteochondrogenesis and Beyond

Peripheral-neuron-like properties of differentiated human dental pulp stem cells (hDPSCs)

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