Oral science and homeostatic medicine最新文献

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NRF2 Stabilization by Isoform-Specific Nuclear Phosphoinositides in Stress Response. 应激反应中核磷酸肌苷对NRF2的稳定作用。

Oral science and homeostatic medicine Pub Date : 2026-03-05 DOI: 10.26599/oshm.2026.9610041

Yiting Tang, Yu Chen, Noah D Carrillo, Vincent L Cryns, Richard A Anderson, Jichao Sun, Mo Chen

{"title":"NRF2 Stabilization by Isoform-Specific Nuclear Phosphoinositides in Stress Response.","authors":"Yiting Tang, Yu Chen, Noah D Carrillo, Vincent L Cryns, Richard A Anderson, Jichao Sun, Mo Chen","doi":"10.26599/oshm.2026.9610041","DOIUrl":"10.26599/oshm.2026.9610041","url":null,"abstract":"Phosphoinositide signaling has long been regarded as a membrane-confined regulatory system; however, emerging evidence reveals a distinct nuclear lipid signaling axis that directly regulates protein stability. A recent study details a previously unrecognized mechanism controlling nuclear factor erythroid 2-related factor 2 (NRF2), demonstrating that oxidative stress induces its stabilization through a nuclear complex composed of type I phosphatidylinositol 4-phosphate 5-kinase γ (PIPKIγ), phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), and small heat shock protein 27 (HSP27). In this pathway, PIPKIγ generates a stably associated nuclear pool of PtdIns(4,5)P2 on NRF2, promoting HSP27 recruitment and protecting NRF2 from proteasomal degradation, independent of the canonical Kelch-like ECH-associated protein 1 (KEAP1) mechanism. This pathway parallels a nuclear phosphoinositide-dependent stabilization paradigm previously described for tumor protein p53 (p53), in which another 5-kinase, type I phosphatidylinositol 4-phosphate 5-kinase α (PIPKIα), mediates p53 stabilization. The isoform-specific engagement of PIP kinases highlights a fundamental principle of nuclear signaling that enables stress-selective transcriptional regulation, exposing new therapeutic vulnerabilities in cancer.","PeriodicalId":521328,"journal":{"name":"Oral science and homeostatic medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13021284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147577584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of two novel variants in homeodomain of MSX1 associated with oligodontia 与少齿症相关的MSX1同源域两个新变异的鉴定

Oral science and homeostatic medicine Pub Date : 2025-09-01 DOI: 10.26599/oshm.2025.9610029

Ting Zeng, Xiuyou Wang, Xu Li, Xin Dong, Xili Qiu, Z. G. Deng, Saimin Pei, Rong Lei, Yuehong Wang, Ling Peng

{"title":"Identification of two novel variants in homeodomain of MSX1 associated with oligodontia","authors":"Ting Zeng, Xiuyou Wang, Xu Li, Xin Dong, Xili Qiu, Z. G. Deng, Saimin Pei, Rong Lei, Yuehong Wang, Ling Peng","doi":"10.26599/oshm.2025.9610029","DOIUrl":"https://doi.org/10.26599/oshm.2025.9610029","url":null,"abstract":"<sec>Introduction This study aimed to identify pathogenic variants in two Chinese families with non-syndromic oligodontia and elucidate their functional consequences. </sec><sec>Methods Whole-exome sequencing (WES) was performed to screen causal variants in two probands. Bioinformatics tools predicted protein structural alterations, immunofluorescence assessed subcellular localization, and dual-luciferase reporter assays quantified transcriptional activity on BMP4 gene. </sec><sec>Results Two variants (c.601G>A, p.E201K; c.657G>A, p.W219*) in the MSX1 gene were identified. Patients with the nonsense variant tended to have a higher mean number of missing teeth than those with the missense variant (11.3 vs 8.7), although the difference was not statistically significant. Structural modeling revealed disruption of the nonsense variant’s tertiary structure, and immunofluorescence confirmed aberrant cytoplasmic mislocalization of the truncated protein. Both variants reduced MSX1 expression (p<0.01) and impaired BMP4 activation (p<0.05), with the nonsense variant showing greater functional impairment. </sec><sec>Conclusions These findings expand the MSX1 variant spectrum in oligodontia. The results indicate that MSX1 mutations may cause oligodontia through disruption of TGF-β/BMP signaling, advancing our understanding of tooth development mechanisms. </sec>","PeriodicalId":521328,"journal":{"name":"Oral science and homeostatic medicine","volume":"1 2","pages":"9610029-9610029"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://file.sciopen.com/sciopen_public/1963784397045366785.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147882005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pip5k1a regulates mandibular homeostasis by orchestrating osteogenesis in mice Pip5k1a通过协调小鼠的成骨调节下颌稳态

Oral science and homeostatic medicine Pub Date : 2025-08-13 DOI: 10.26599/oshm.2025.9610026

Bo Zhou, Yao Feng, Jinchu Liang, Zihan Lu, Shaohui Zhang, Xuan Wang, Ran Zhang, Shimin Shuai, Songlin Wang, Mo Chen

{"title":"Pip5k1a regulates mandibular homeostasis by orchestrating osteogenesis in mice","authors":"Bo Zhou, Yao Feng, Jinchu Liang, Zihan Lu, Shaohui Zhang, Xuan Wang, Ran Zhang, Shimin Shuai, Songlin Wang, Mo Chen","doi":"10.26599/oshm.2025.9610026","DOIUrl":"https://doi.org/10.26599/oshm.2025.9610026","url":null,"abstract":"Mandibular homeostasis depends on mesenchymal stromal cells (MSCs), whose site-specific characteristics critically influence osteogenesis. While phosphoinositide signaling has been extensively studied in limb osteogenesis, its role in mandibular homeostasis remains poorly understood. Despite shared mechanisms underlying hard tissue homeostasis, this study uncovers a distinct regulatory function for Pip5k1a in mandibular osteogenesis, contrasting the previously established role of Pip5k1c in limb osteogenesis. Single-cell transcriptomic analysis revealed unique transcriptional profiles between mandibular MSCs (MdMSCs) and limb MSCs (LbMSCs), with Pip5k1a being highly expressed in MdMSCs and their osteo-lineages. Functional assays demonstrated that Pip5k1a inhibition significantly reduced osteoblastic differentiation while promoting adipogenesis in MdMSCs, underscoring its essential role in osteogenic fate determination. Enrichment of Pip5k1a expression in the mandibular periosteum and endosteum further supports its specialized role in mandibular biology. These findings highlight site-specific molecular mechanisms in bone remodeling and position Pip5k1a as a promising therapeutic target for mandibular bone diseases, such as periodontitis and fractures.","PeriodicalId":521328,"journal":{"name":"Oral science and homeostatic medicine","volume":"1 3","pages":"9610026-9610026"},"PeriodicalIF":0.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147895179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2