Application of Antibodies to Neuronally Expressed Nogo-A Increases Neuronal Survival and Neurite Outgrowth

Nagaraj, Vini; Theis, Thomas L.; Johal, Anmol S.; Seth, Arihant; Gore, Jada; Arsha, Neha; Patel, Mukti; Hao, Baixia; Kurian, Nikki; Schachner, Melitta

doi:10.3390/ijms21155417

Cited by 8 publications

(3 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Due to the beneficial effects of Nogo-A inactivation for the regeneration of injured nerve fibers [ 91 , 92 , 93 , 94 ], this molecule is the target in clinical trials aiming at the treatment of severe spinal cord lesions [ 72 ]. Antibodies or decoy receptors (‘Nogo-traps’) that block the function of Nogo-A could be tools of high potential for these therapies.…”

Section: Discussionmentioning

confidence: 99%

Nogo-A Regulates the Fate of Human Dental Pulp Stem Cells toward Osteogenic, Adipogenic, and Neurogenic Differentiation

Lai

Shen

Balic

et al. 2022

Cells

View full text Add to dashboard Cite

Human teeth are highly innervated organs that contain a variety of mesenchymal stem cell populations that could be used for cell-based regenerative therapies. Specific molecules are often used in these treatments to favorably modulate the function and fate of stem cells. Nogo-A, a key regulator of neuronal growth and differentiation, is already used in clinical tissue regeneration trials. While the functions of Nogo-A in neuronal tissues are extensively explored, its role in teeth still remains unknown. In this work, we first immunohistochemically analyzed the distribution of Nogo-A protein in the dental pulp of human teeth. Nogo-A is localized in a variety of cellular and structural components of the dental pulp, including odontoblasts, fibroblasts, neurons and vessels. We also cross-examined Nogo expression in the various pulp cell clusters in a single cell RNA sequencing dataset of human dental pulp, which showed high levels of expression in all cell clusters, including that of stem cells. We then assessed the role of Nogo-A on the fate of human dental pulp stem cells and their differentiation capacity in vitro. Using immunostaining, Alizarin Red S, Nile Red and Oil Red O staining we showed that Nogo-A delayed the differentiation of cultured dental pulp stem cells toward the osteogenic, adipogenic and neurogenic lineages, while addition of the blocking anti-Nogo-A antibody had opposite effects. These results were further confirmed by qRT-PCR, which demonstrated overexpression of genes involved in osteogenic (RUNX2, ALP, SP7/OSX), adipogenic (PPAR-γ2, LPL) and neurogenic (DCX, TUBB3, NEFL) differentiation in the presence of the anti-Nogo-A antibody. Conversely, the osteogenic and adipogenic genes were downregulated by Nogo-A. Taken together, our results show that the functions of Nogo-A are not restricted to neuronal cells but are extended to other cell populations, including dental pulp stem cells. We show that Nogo-A regulates their fates toward osteogenic, adipogenic and neurogenic differentiation, thus indicating its potential use in clinics.

show abstract

Section: Discussionmentioning

confidence: 99%

Nogo-A Regulates the Fate of Human Dental Pulp Stem Cells toward Osteogenic, Adipogenic, and Neurogenic Differentiation

Lai

Shen

Balic

et al. 2022

Cells

View full text Add to dashboard Cite

show abstract

“…Due to the beneficial effects of Nogo-A inactivation for the regeneration of injured nerve fibers 91–94 , this molecule is the target in clinical trials aiming at the treatment of severe spinal cord lesions 72 . Antibodies or decoy receptors (‘Nogo-traps’) that block the function of Nogo-A could be tools of high potential for these therapies.…”

Section: Discussionmentioning

confidence: 99%

Nogo-A regulates the fate of human dental pulp stem cells towards osteogenic, adipogenic, and neurogenic differentiation

Shen

Lai

Balic

et al. 2022

Preprint

View full text Add to dashboard Cite

Human teeth are highly innervated organs that contain a variety of mesenchymal stem cell populations that could be used for cell-based regenerative therapies. Specific molecules are often used in these treatments to favorably modulate stem cells function and fate. Nogo-A, a key regulator of neuronal growth and differentiation, is already used in clinical tissue regeneration trials. While the functions of Nogo-A in neuronal tissues are extensively explored, its role in teeth still remains unknown. In this work, we first immunohistochemically analyzed the distribution of Nogo-A protein in the dental pulp of human teeth. Nogo-A is localized in a variety of cellular and structural components of the dental pulp, including odontoblasts, fibroblasts, neurons and vessels. We also cross-examined Nogo expression in the various pulp cell clusters in a single cell RNA sequencing dataset of human dental pulp, which showed high levels of expression in all cell clusters, including that of stem cells. We then assessed the role of Nogo-A on the fate of human dental pulp stem cells and their differentiation capacity in vitro. Using immunostaining, Alizarin Red S and Oil Red O staining we showed that Nogo-A delayed the differentiation of cultured dental pulp stem cells towards the osteogenic, adipogenic and neurogenic lineages, while addition of the blocking anti-Nogo-A antibody had opposite effects. These results were further confirmed by qRT-PCR, which demonstrated overexpression of genes involved in osteogenic (RUNX2, ALP, SP7/OSX), adipogenic (PPAR-γ2, LPL) and neurogenic (DCX, TUBB3, NEFL) differentiation in presence of the anti-Nogo-A antibody. Conversely, the osteogenic and adipogenic genes were downregulated by Nogo-A. Taken together, our results show that the functions of Nogo-A are not restricted to neuronal cells, but are extended to other cell populations, including dental pulp stem cells. We show that Nogo-A regulates their fates towards osteogenic, adipogenic and neurogenic differentiation, thus indicating its potential use in the clinics.

show abstract

“…It has been reported in previous study that Shenfu injection might show anti-inflammatory or anti-oxidative effects on myocardial ischemia-reperfusion injury, sepsis, and acute lung injury in rats [20][21][22][23]. Nogo-NgR was associated with axonal regeneration, and inhibition of Nogo-NgR could attenuate nerve injury in previous studies [24][25][26]. Results of our study indicated that Shenfu injection may suppress CA-induced Nogo-NgR up-expression in the hippocampus of rats and improve neurological function, which suggested that Shenfu injection might protect brain in rats with CA and be helpful for axonal regeneration through Nogo/NgR pathway.…”

Section: Discussionmentioning

confidence: 99%

Shenfu Injection Protects Brain Injury in Rats with Cardiac Arrest through Nogo/NgR Pathway

Deng

Tang

Tuo

et al. 2022

Analytical Cellular Pathology

View full text Add to dashboard Cite

The effect of Shenfu injection on brain injury after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) along with the underlying mechanism of axonal regeneration was explored. CA/CPR model in rats was established for subsequent experiments. A total of 160 rats were randomly divided into sham group, model group, conventional western medicine (CWM) group, Shenfu group, and antagonist group ( n = 32 per group). After 3 hours, 24 hours, 3 days, and 7 days of drug administration, the modified Neurological Severity Score tests were performed. The ultrastructure of the brain and hippocampus was observed by electron microscopy. Real-time quantitative polymerase chain reaction (PCR), western blotting, and immunohistochemistry were used to detect Nogo receptor (NgR) expression in the hippocampus and cerebral cortex, and Nogo–NgR expression in CA/CPR model. Neurological deficits in the model group were severe at 3 hours, 24 hours, 3 days, and 7 days after the recovery of natural circulation, whereas the neurological deficits in CWM, antagonist, and Shenfu group were relatively mild. The ultrastructure of neuronal cells in Shenfu group had relatively complete cell membranes and more vesicles than those in the model group. The results of PCR and western blotting showed lower messenger ribonucleic acid and protein expression of NgR in Shenfu group than the model group and CWM group. Immunohistochemical examination indicated a reduction of Nogo–NgR expression in Shenfu group and antagonist group. Our results suggested that Shenfu injection reduced brain injury by attenuating Nogo–NgR signaling pathway and promoting axonal regeneration.

show abstract

Application of Antibodies to Neuronally Expressed Nogo-A Increases Neuronal Survival and Neurite Outgrowth

Cited by 8 publications

References 34 publications

Nogo-A Regulates the Fate of Human Dental Pulp Stem Cells toward Osteogenic, Adipogenic, and Neurogenic Differentiation

Nogo-A Regulates the Fate of Human Dental Pulp Stem Cells toward Osteogenic, Adipogenic, and Neurogenic Differentiation

Nogo-A regulates the fate of human dental pulp stem cells towards osteogenic, adipogenic, and neurogenic differentiation

Shenfu Injection Protects Brain Injury in Rats with Cardiac Arrest through Nogo/NgR Pathway

Contact Info

Product

Resources

About