{"doi":"10.1111/dgd.12745","title":"Expression of nitric oxide synthases in rat odontoblasts and the role of nitric oxide in odontoblastic differentiation of rat dental papilla cells","abstract":"<jats:title>Abstract</jats:title><jats:p>As precursor cells of odontoblasts, dental papilla cells (DPCs) form the dentin–pulp complex during tooth development. Nitric oxide (NO) regulates the functions of multiple cells and organ tissues, including stem cell differentiation and bone formation. In this paper, we explored the involvement of NO in odontoblastic differentiation. We verified the expression of NO synthase (NOS) in rat odontoblasts by nicotinamide adenine dinucleotide phosphate–diaphorase (NADPH‐d) staining and immunohistochemistry in vivo. The expression of all three NOS isoforms in rat DPCs was confirmed by quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR), immunofluorescence, and western blotting in vitro. The expression of neuronal NOS and endothelial NOS was upregulated during the odontoblastic differentiation of DPCs. Inhibition of NOS function by NOS inhibitor <jats:sc>l</jats:sc>‐<jats:italic>N</jats:italic><jats:sup>G</jats:sup>‐monomethyl arginine (L‐NMMA) resulted in reduced formation of mineralized nodules and expression of dentin sialophosphoprotein (DSPP) and dentin matrix protein (DMP1) during DPC differentiation. The NO donor <jats:italic>S</jats:italic>‐nitroso‐<jats:italic>N</jats:italic>‐acetylpenicillamine (SNAP, 0.1, 1, 10, and 100 μM) promoted the viability of DPCs. Extracellular matrix mineralization and odontogenic markers expression were elevated by SNAP at low concentrations (0.1, 1, and 10 μM) and suppressed at high concentration (100 μM). Blocking the generation of cyclic guanosine monophosphate (cGMP) with 1<jats:italic>H</jats:italic>‐(1,2,4)oxadiazolo‐(4,3‐a)quinoxalin‐1‐one (ODQ) abolished the positive influence of SNAP on the odontoblastic differentiation of DPCs. These findings demonstrate that NO regulates the odontoblastic differentiation of DPCs, thereby influencing dentin formation and tooth development.</jats:p>","journal":"Development, Growth &amp; Differentiation","year":2021,"id":687792,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1338053,"name":"Yu Kong","orcid":"0000-0001-5690-8358","position":1,"is_corresponding":false},{"id":1535517,"name":"Wenguo Fan","orcid":null,"position":2,"is_corresponding":false},{"id":1434570,"name":"Jun Kang","orcid":"0009-0001-7883-0798","position":3,"is_corresponding":false},{"id":1796817,"name":"Haoling Chen","orcid":null,"position":4,"is_corresponding":false},{"id":1743828,"name":"Hongwen He","orcid":null,"position":5,"is_corresponding":false},{"id":79251,"name":"Fang Huang","orcid":"0000-0003-3408-8090","position":6,"is_corresponding":false},{"id":865192,"name":"Tong Yan","orcid":"0000-0002-5903-5692","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Expression of nitric oxide synthases in rat odontoblasts and the role of nitric oxide in odontoblastic differentiation of rat dental papilla cells","abstract":"<jats:title>Abstract</jats:title><jats:p>As precursor cells of odontoblasts, dental papilla cells (DPCs) form the dentin–pulp complex during tooth development. Nitric oxide (NO) regulates the functions of multiple cells and organ tissues, including stem cell differentiation and bone formation. In this paper, we explored the involvement of NO in odontoblastic differentiation. We verified the expression of NO synthase (NOS) in rat odontoblasts by nicotinamide adenine dinucleotide phosphate–diaphorase (NADPH‐d) staining and immunohistochemistry in vivo. The expression of all three NOS isoforms in rat DPCs was confirmed by quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR), immunofluorescence, and western blotting in vitro. The expression of neuronal NOS and endothelial NOS was upregulated during the odontoblastic differentiation of DPCs. Inhibition of NOS function by NOS inhibitor <jats:sc>l</jats:sc>‐<jats:italic>N</jats:italic><jats:sup>G</jats:sup>‐monomethyl arginine (L‐NMMA) resulted in reduced formation of mineralized nodules and expression of dentin sialophosphoprotein (DSPP) and dentin matrix protein (DMP1) during DPC differentiation. The NO donor <jats:italic>S</jats:italic>‐nitroso‐<jats:italic>N</jats:italic>‐acetylpenicillamine (SNAP, 0.1, 1, 10, and 100 μM) promoted the viability of DPCs. Extracellular matrix mineralization and odontogenic markers expression were elevated by SNAP at low concentrations (0.1, 1, and 10 μM) and suppressed at high concentration (100 μM). Blocking the generation of cyclic guanosine monophosphate (cGMP) with 1<jats:italic>H</jats:italic>‐(1,2,4)oxadiazolo‐(4,3‐a)quinoxalin‐1‐one (ODQ) abolished the positive influence of SNAP on the odontoblastic differentiation of DPCs. These findings demonstrate that NO regulates the odontoblastic differentiation of DPCs, thereby influencing dentin formation and tooth development.</jats:p>","is_dataset_classified":null,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"34411285","pmcid":null,"openalex_id":"https://openalex.org/W3194203986","authors":[],"funders":[{"funder_name":"National Natural Science Foundation of China","grant_id":"81771098","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"81870737","title":null},{"funder_name":"Natural Science Foundation of Guangdong Province","grant_id":"2021A1515011779","title":null},{"funder_name":"Guangdong Financial Fund for High-Caliber Hospital Construction","grant_id":"174-2018-XMZC-0001-03-0125/D-02","title":null}],"total_grants":4,"fwci":0.1142,"citation_percentile":0.43382077,"influential_citations":0,"citation_trend":[{"year":2024,"count":1},{"year":2025,"count":1},{"year":2026,"count":1}],"oa_status":"bronze","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/dgd.12745","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/dgd.12745","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/dgd.12745","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full-xml/10.1111/dgd.12745","host_type":"publisher"},{"url":"https://doi.org/10.1111/dgd.12745","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/34411285","host_type":"repository"}],"fields_of_study":["Nitric Oxide and Endothelin Effects","Aldose Reductase and Taurine","Neuroscience of respiration and sleep"],"mesh_terms":["Animals","Cell Differentiation","Cells, Cultured","Dental Papilla","Dental Pulp","Nitric Oxide","Odontoblasts","Nitric Oxide Synthase","Rats"],"keywords":["Odontoblast","Dentin sialophosphoprotein","Dentinogenesis","Chemistry","Dental papilla","Cell biology","Nitric oxide synthase","Nitric oxide","Cellular differentiation","Soluble guanylyl cyclase","Extracellular matrix","Cyclic guanosine monophosphate","Molecular biology","Dentin","Biochemistry","Biology","Pathology","Differentiation","cGMP","Dental papilla cell","Odontoblasts"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Clean water and sanitation"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-18T22:44:41.359170Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}