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GenAI synthesis of histopathological images from Raman imaging for intraoperative tongue squamous cell carcinoma assessment GenAI 从拉曼成像合成组织病理学图像,用于术中舌鳞状细胞癌评估
IF 14.9 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-01-26 DOI: 10.1038/s41368-025-00346-y
Bing Yan, Zhining Wen, Lili Xue, Tianyi Wang, Zhichao Liu, Wulin Long, Yi Li, Runyu Jing

The presence of a positive deep surgical margin in tongue squamous cell carcinoma (TSCC) significantly elevates the risk of local recurrence. Therefore, a prompt and precise intraoperative assessment of margin status is imperative to ensure thorough tumor resection. In this study, we integrate Raman imaging technology with an artificial intelligence (AI) generative model, proposing an innovative approach for intraoperative margin status diagnosis. This method utilizes Raman imaging to swiftly and non-invasively capture tissue Raman images, which are then transformed into hematoxylin-eosin (H&E)-stained histopathological images using an AI generative model for histopathological diagnosis. The generated H&E-stained images clearly illustrate the tissue’s pathological conditions. Independently reviewed by three pathologists, the overall diagnostic accuracy for distinguishing between tumor tissue and normal muscle tissue reaches 86.7%. Notably, it outperforms current clinical practices, especially in TSCC with positive lymph node metastasis or moderately differentiated grades. This advancement highlights the potential of AI-enhanced Raman imaging to significantly improve intraoperative assessments and surgical margin evaluations, promising a versatile diagnostic tool beyond TSCC.

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引用次数: 0
The impact of aging on neutrophil functions and the contribution to periodontitis 衰老对中性粒细胞功能的影响及对牙周炎的贡献
IF 14.9 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-01-16 DOI: 10.1038/s41368-024-00332-w
Zi Wang, Anish Saxena, Wenbo Yan, Silvia M. Uriarte, Rafael Siqueira, Xin Li

The increasing aging population and aging-associated diseases have become a global issue for decades. People over 65 show an increased prevalence and greater severity of periodontitis, which poses threats to overall health. Studies have demonstrated a significant association between aging and the dysfunction of neutrophils, critical cells in the early stages of periodontitis, and their crosstalk with macrophages and T and B lymphocytes to establish the periodontal lesion. Neutrophils differentiate and mature in the bone marrow before entering the circulation; during an infection, they are recruited to infected tissues guided by the signal from chemokines and cytokines to eliminate invading pathogens. Neutrophils are crucial in maintaining a balanced response between host and microbes to prevent periodontal diseases in periodontal tissues. The impacts of aging on neutrophils’ chemotaxis, anti-microbial function, cell activation, and lifespan result in impaired neutrophil functions and excessive neutrophil activation, which could influence periodontitis course. We summarize the roles of neutrophils in periodontal diseases and the aging-related impacts on neutrophil functional responses. We also explore the underlying mechanisms that can contribute to periodontitis manifestation in aging. This review could help us better understand the pathogenesis of periodontitis, which could offer novel therapeutic targets for periodontitis.

几十年来,人口老龄化和老龄化相关疾病已成为一个全球性问题。65岁以上的人牙周炎的发病率和严重程度都有所增加,这对整体健康构成了威胁。研究表明,衰老与中性粒细胞功能障碍之间存在显著关联,中性粒细胞是牙周炎早期的关键细胞,它们与巨噬细胞、T淋巴细胞和B淋巴细胞相互作用,形成牙周病变。中性粒细胞在进入循环之前在骨髓中分化和成熟;在感染期间,它们在趋化因子和细胞因子信号的引导下被招募到感染组织中,以消除入侵的病原体。中性粒细胞在维持宿主和微生物之间的平衡反应以预防牙周组织中的牙周疾病中起着至关重要的作用。衰老对中性粒细胞趋化性、抗菌功能、细胞活化和寿命的影响导致中性粒细胞功能受损和中性粒细胞活化过度,从而影响牙周炎的病程。本文综述了中性粒细胞在牙周病中的作用以及衰老对中性粒细胞功能反应的影响。我们还探讨了可能导致牙周炎在衰老过程中表现的潜在机制。这一综述有助于我们更好地了解牙周炎的发病机制,为牙周炎的治疗提供新的靶点。
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引用次数: 0
Tongue squamous cell carcinoma-targeting Au-HN-1 nanosystem for CT imaging and photothermal therapy 用于 CT 成像和光热疗法的舌鳞癌靶向 Au-HN-1 纳米系统
IF 14.9 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-01-14 DOI: 10.1038/s41368-024-00343-7
Ming Hao, Xingchen Li, Xinxin Zhang, Boqiang Tao, He Shi, Jianing Wu, Yuyang Li, Xiang Li, Shuangji Li, Han Wu, Jingcheng Xiang, Dongxu Wang, Weiwei Liu, Guoqing Wang

Tongue squamous cell carcinoma (TSCC) is a prevalent malignancy that afflicts the head and neck area and presents a high incidence of metastasis and invasion. Accurate diagnosis and effective treatment are essential for enhancing the quality of life and the survival rates of TSCC patients. The current treatment modalities for TSCC frequently suffer from a lack of specificity and efficacy. Nanoparticles with diagnostic and photothermal therapeutic properties may offer a new approach for the targeted therapy of TSCC. However, inadequate accumulation of photosensitizers at the tumor site diminishes the efficacy of photothermal therapy (PTT). This study modified gold nanodots (AuNDs) with the TSCC-targeting peptide HN-1 to improve the selectivity and therapeutic effects of PTT. The Au-HN-1 nanosystem effectively targeted the TSCC cells and was rapidly delivered to the tumor tissues compared to the AuNDs. The enhanced accumulation of photosensitizing agents at tumor sites achieved significant PTT effects in a mouse model of TSCC. Moreover, owing to its stable long-term fluorescence and high X-ray attenuation coefficient, the Au-HN-1 nanosystem can be used for fluorescence and computed tomography imaging of TSCC, rendering it useful for early tumor detection and accurate delineation of surgical margins. In conclusion, Au-HN-1 represents a promising nanomedicine for imaging-based diagnosis and targeted PTT of TSCC.

舌鳞状细胞癌(TSCC)是一种常见的头颈部恶性肿瘤,其转移和侵袭的发生率很高。准确诊断和有效治疗对于提高 TSCC 患者的生活质量和生存率至关重要。目前治疗 TSCC 的方法往往缺乏特异性和有效性。具有诊断和光热治疗特性的纳米粒子可为 TSCC 的靶向治疗提供一种新方法。然而,光敏剂在肿瘤部位的积累不足会降低光热疗法(PTT)的疗效。本研究用TSCC靶向肽HN-1修饰了金纳米点(AuNDs),以提高PTT的选择性和治疗效果。与 AuNDs 相比,Au-HN-1 纳米系统能有效靶向 TSCC 细胞,并能快速输送到肿瘤组织。在 TSCC 小鼠模型中,光敏剂在肿瘤部位的积累得到了增强,从而实现了显著的 PTT 效果。此外,由于 Au-HN-1 纳米系统具有长期稳定的荧光和较高的 X 射线衰减系数,因此可用于 TSCC 的荧光和计算机断层扫描成像,从而有助于早期肿瘤检测和准确划分手术边缘。总之,Au-HN-1 是一种很有前景的纳米药物,可用于 TSCC 的成像诊断和靶向 PTT。
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引用次数: 0
Adhesive and injectable hydrogel microspheres for NRF2-mediated periodontal bone regeneration. 粘附和可注射水凝胶微球用于nrf2介导的牙周骨再生。
IF 10.8 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-01-10 DOI: 10.1038/s41368-024-00340-w
Yu Wang, Shanshan Jin, Yaru Guo, Yilong Lu, Xuliang Deng

Regenerating periodontal bone defect surrounding periodontal tissue is crucial for orthodontic or dental implant treatment. The declined osteogenic ability of periodontal ligament stem cells (PDLSCs) induced by inflammation stimulus contributes to reduced capacity to regenerate periodontal bone, which brings about a huge challenge for treating periodontitis. Here, inspired by the adhesive property of mussels, we have created adhesive and mineralized hydrogel microspheres loaded with traditional compound cordycepin (MMS-CY). MMS-CY could adhere to the surface of alveolar bone, then promote the migration capacity of PDLSCs and thus recruit them to inflammatory periodontal tissues. Furthermore, MMS-CY rescued the impaired osteogenesis and ligament-forming capacity of PDLSCs, which were suppressed by the inflammation stimulus. Moreover, MMS-CY also displayed the excellent inhibitory effect on the osteoclastic activity. Mechanistically, MMS-CY inhibited the premature senescence induced by the inflammation stimulus through the nuclear factor erythroid 2-related factor (NRF2) pathway and reducing the DNA injury. Utilizing in vivo rat periodontitis model, MMS-CY was demonstrated to enhance the periodontal bone regeneration by improving osteogenesis and inhibiting the osteoclastic activity. Altogether, our study indicated that the multi-pronged approach is promising to promote the periodontal bone regeneration in periodontitis condition by reducing the inflammation-induced stem cell senescence and maintaining bone homeostasis.

再生牙周骨缺损周围的牙周组织是至关重要的正畸或种植牙治疗。炎症刺激诱导的牙周韧带干细胞(periodontal ligament stem cells, PDLSCs)成骨能力下降,导致牙周骨再生能力下降,给牙周炎的治疗带来巨大挑战。在这里,受贻贝的粘附特性的启发,我们创造了装载传统复方冬虫夏草素(MMS-CY)的粘附和矿化水凝胶微球。MMS-CY可以粘附在牙槽骨表面,促进PDLSCs的迁移能力,从而将其招募到炎症性牙周组织。此外,MMS-CY恢复了被炎症刺激抑制的PDLSCs受损的成骨和韧带形成能力。此外,MMS-CY对破骨细胞活性也表现出良好的抑制作用。在机制上,MMS-CY通过核因子红系2相关因子(NRF2)途径抑制炎症刺激诱导的早衰,减少DNA损伤。利用体内大鼠牙周炎模型,证实MMS-CY通过促进成骨和抑制破骨细胞活性来促进牙周骨再生。总之,我们的研究表明,多管齐下的方法有望通过减少炎症诱导的干细胞衰老和维持骨稳态来促进牙周炎条件下的牙周骨再生。
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引用次数: 0
Expert consensus on pulpotomy in the management of mature permanent teeth with pulpitis 专家一致同意牙髓切开术治疗成熟恒牙伴牙髓炎
IF 14.9 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-01-07 DOI: 10.1038/s41368-024-00333-9
Lu Zhang, Chen Lin, Zhuo Chen, Lin Yue, Qing Yu, Benxiang Hou, Junqi Ling, Jingping Liang, Xi Wei, Wenxia Chen, Lihong Qiu, Jiyao Li, Yumei Niu, Zhengmei Lin, Lei Cheng, Wenxi He, Xiaoyan Wang, Dingming Huang, Zhengwei Huang, Weidong Niu, Qi Zhang, Chen Zhang, Deqin Yang, Jinhua Yu, Jin Zhao, Yihuai Pan, Jingzhi Ma, Shuli Deng, Xiaoli Xie, Xiuping Meng, Jian Yang, Xuedong Zhou, Zhi Chen

Pulpotomy, which belongs to vital pulp therapy, has become a strategy for managing pulpitis in recent decades. This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes. Pulpotomy is categorized into partial pulpotomy (PP), the removal of a partial segment of the coronal pulp tissue, and full pulpotomy (FP), the removal of whole coronal pulp, which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth. Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality, the overall treatment plan, the patient’s general health status, and pulp inflammation reassessment during operation. This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics, Chinese Stomatological Association. It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment (RCT) on mature permanent teeth with pulpitis from a biological basis, the development of capping biomaterial, and the diagnostic considerations to evidence-based medicine. This expert statement intends to provide a clinical protocol of pulpotomy, which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.

牙髓切开术是一种重要的牙髓治疗方法,近几十年来已成为治疗牙髓炎的一种策略。这种微创治疗反映了对保留健康牙髓和优化以患者为中心的长期结果的认识。牙髓切开术分为部分牙髓切开术(PP)和完全牙髓切开术(FP),前者切除部分冠状牙髓组织,后者切除整个冠状牙髓,然后将生物材料应用于剩余的牙髓组织,最终修复牙齿。切除或保留牙髓组织的数量取决于牙髓活力的诊断、整体治疗计划、患者的一般健康状况和术中对牙髓炎症的重新评估。本声明代表了由中国口腔医学会牙髓学分会召集的专家委员会的共识。本文从生物学基础、封盖生物材料的发展以及循证医学的诊断考虑等方面阐述了目前支持牙髓切开术作为成熟恒牙牙髓炎根管治疗(RCT)的潜在替代方法的证据。本专家声明旨在提供一个临床方案髓切开术,这有助于医生选择最佳的程序,并增加他们的信心在这个快速发展的领域。
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引用次数: 0
Effect of regional crosstalk between sympathetic nerves and sensory nerves on temporomandibular joint osteoarthritic pain 交感神经与感觉神经局部串扰对颞下颌关节骨关节炎疼痛的影响
IF 14.9 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-01-07 DOI: 10.1038/s41368-024-00336-6
Zhangyu Ma, Qianqian Wan, Wenpin Qin, Wen Qin, Janfei Yan, Yina Zhu, Yuzhu Wang, Yuxuan Ma, Meichen Wan, Xiaoxiao Han, Haoyan Zhao, Yuxuan Hou, Franklin R. Tay, Lina Niu, Kai Jiao

Temporomandibular joint osteoarthritis (TMJ-OA) is a common disease often accompanied by pain, seriously affecting physical and mental health of patients. Abnormal innervation at the osteochondral junction has been considered as a predominant origin of arthralgia, while the specific mechanism mediating pain remains unclear. To investigate the underlying mechanism of TMJ-OA pain, an abnormal joint loading model was used to induce TMJ-OA pain. We found that during the development of TMJ-OA, the increased innervation of sympathetic nerve of subchondral bone precedes that of sensory nerves. Furthermore, these two types of nerves are spatially closely associated. Additionally, it was discovered that activation of sympathetic neural signals promotes osteoarthritic pain in mice, whereas blocking these signals effectively alleviates pain. In vitro experiments also confirmed that norepinephrine released by sympathetic neurons promotes the activation and axonal growth of sensory neurons. Moreover, we also discovered that through releasing norepinephrine, regional sympathetic nerves of subchondral bone were found to regulate growth and activation of local sensory nerves synergistically with other pain regulators. This study identified the role of regional sympathetic nerves in mediating pain in TMJ-OA. It sheds light on a new mechanism of abnormal innervation at the osteochondral junction and the regional crosstalk between peripheral nerves, providing a potential target for treating TMJ-OA pain.

颞下颌关节骨性关节炎(TMJ-OA)是一种常见病,常伴有疼痛,严重影响患者身心健康。骨软骨交界处的神经支配异常被认为是关节痛的主要起源,而介导疼痛的具体机制尚不清楚。为了探讨TMJ-OA疼痛的潜在机制,我们采用异常关节负荷模型诱导TMJ-OA疼痛。我们发现,在TMJ-OA的发展过程中,软骨下骨交感神经支配的增加先于感觉神经支配的增加。此外,这两种类型的神经在空间上密切相关。此外,还发现交感神经信号的激活可促进小鼠骨关节炎疼痛,而阻断这些信号可有效减轻疼痛。体外实验也证实了交感神经元释放的去甲肾上腺素促进感觉神经元的激活和轴突生长。此外,我们还发现,通过释放去甲肾上腺素,软骨下骨的区域交感神经与其他疼痛调节剂协同调节局部感觉神经的生长和激活。本研究确定了区域交感神经在TMJ-OA疼痛介导中的作用。它揭示了骨软骨交界处异常神经支配和周围神经间区域串扰的新机制,为治疗TMJ-OA疼痛提供了潜在的靶点。
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引用次数: 0
Host-microbe computational proteomic landscape in oral cancer revealed key functional and metabolic pathways between Fusobacterium nucleatum and cancer progression 口腔癌中宿主-微生物计算蛋白质组学景观揭示了核梭杆菌与癌症进展之间的关键功能和代谢途径
IF 14.9 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-01-02 DOI: 10.1038/s41368-024-00326-8
Camila Paz Muñoz-Grez, Mabel Angélica Vidal, Tamara Beatriz Rojas, Luciano Esteban Ferrada, Felipe Andrés Zuñiga, Agustin Andrés Vera, Sergio Andrés Sanhueza, Romina Andrea Quiroga, Camilo Daniel Cabrera, Barbara Evelyn Antilef, Ricardo Andrés Cartes, Milovan Paolo Acevedo, Marco Andrés Fraga, Pedro Felipe Alarcón-Zapata, Mauricio Alejandro Hernández, Alexis Marcelo Salas-Burgos, Francisco Tapia-Belmonte, Milly Loreto Yáñez, Erick Marcelo Riquelme, Wilfredo Alejandro González, Cesar Andrés Rivera, Angel Alejandro Oñate, Liliana Ivonne Lamperti, Estefanía Nova-Lamperti

Oral squamous cell carcinoma (OSCC) is the most common manifestation of oral cancer. It has been proposed that periodontal pathogens contribute to OSCC progression, mainly by their virulence factors. However, the main periodontal pathogen and its mechanism to modulate OSCC cells remains not fully understood. In this study we investigate the main host-pathogen pathways in OSCC by computational proteomics and the mechanism behind cancer progression by the oral microbiome. The main host-pathogen pathways were analyzed in the secretome of biopsies from patients with OSCC and healthy controls by mass spectrometry. Then, functional assays were performed to evaluate the host-pathogen pathways highlighted in oral cancer. Host proteins associated with LPS response, cell migration/adhesion, and metabolism of amino acids were significantly upregulated in the human cancer proteome, whereas the complement cascade was downregulated in malignant samples. Then, the microbiome analysis revealed large number and variety of peptides from Fusobacterium nucleatum (F. nucleatum) in OSCC samples, from which several enzymes from the L-glutamate degradation pathway were found, indicating that L-glutamate from cancer cells is used as an energy source, and catabolized into butyrate by the bacteria. In fact, we observed that F. nucleatum modulates the cystine/glutamate antiporter in an OSCC cell line by increasing SLC7A11 expression, promoting L-glutamate efflux and favoring bacterial infection. Finally, our results showed that F. nucleatum and its metabolic derivates promote tumor spheroids growth, spheroids-derived cell detachment, epithelial-mesenchymal transition and Galectin-9 upregulation. Altogether, F. nucleatum promotes pro-tumoral mechanism in oral cancer.

口腔鳞状细胞癌(Oral squamous cell carcinoma, OSCC)是最常见的口腔癌。已经提出牙周病原体主要通过其毒力因子促进OSCC的进展。然而,主要的牙周病原体及其调节OSCC细胞的机制尚不完全清楚。在这项研究中,我们通过计算蛋白质组学研究了OSCC的主要宿主-病原体途径,以及口腔微生物群导致癌症进展的机制。用质谱法分析了OSCC患者和健康对照活检组织的主要宿主-病原体途径。然后,进行功能分析以评估口腔癌中突出的宿主-病原体途径。与LPS反应、细胞迁移/粘附和氨基酸代谢相关的宿主蛋白在人类癌症蛋白质组中显著上调,而在恶性样本中补体级联则下调。然后,微生物组分析显示,在OSCC样品中发现了大量来自核梭菌(F. nucleatum)的肽,其中发现了l -谷氨酸降解途径的几种酶,表明癌细胞中的l -谷氨酸被用作能量来源,并被细菌分解代谢为丁酸盐。事实上,我们观察到F. nucleatum通过增加SLC7A11表达、促进l -谷氨酸外排和促进细菌感染来调节OSCC细胞系中的胱氨酸/谷氨酸反转运蛋白。最后,我们的研究结果表明,核梭菌及其代谢衍生物促进肿瘤类球生长、类球细胞分离、上皮-间质转化和半乳糖凝集素-9上调。总之,核梭菌促进口腔癌的促瘤机制。
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引用次数: 0
Expert consensus on apical microsurgery 根尖显微外科专家共识
IF 14.9 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-01-02 DOI: 10.1038/s41368-024-00334-8
Hanguo Wang, Xin Xu, Zhuan Bian, Jingping Liang, Zhi Chen, Benxiang Hou, Lihong Qiu, Wenxia Chen, Xi Wei, Kaijin Hu, Qintao Wang, Zuhua Wang, Jiyao Li, Dingming Huang, Xiaoyan Wang, Zhengwei Huang, Liuyan Meng, Chen Zhang, Fangfang Xie, Di Yang, Jinhua Yu, Jin Zhao, Yihuai Pan, Shuang Pan, Deqin Yang, Weidong Niu, Qi Zhang, Shuli Deng, Jingzhi Ma, Xiuping Meng, Jian Yang, Jiayuan Wu, Yi Du, Junqi Ling, Lin Yue, Xuedong Zhou, Qing Yu

Apical microsurgery is accurate and minimally invasive, produces few complications, and has a success rate of more than 90%. However, due to the lack of awareness and understanding of apical microsurgery by dental general practitioners and even endodontists, many clinical problems remain to be overcome. The consensus has gathered well-known domestic experts to hold a series of special discussions and reached the consensus. This document specifies the indications, contraindications, preoperative preparations, operational procedures, complication prevention measures, and efficacy evaluation of apical microsurgery and is applicable to dentists who perform apical microsurgery after systematic training.

根尖显微手术准确、微创,并发症少,成功率达90%以上。然而,由于牙科全科医生甚至牙髓医生对根尖显微外科的认识和了解不足,许多临床问题仍有待克服。该共识汇集了国内知名专家,举行了一系列专题讨论,达成了共识。本文件规定了根尖显微外科手术的适应证、禁忌症、术前准备、操作程序、并发症预防措施、疗效评价等,适用于经过系统培训后从事根尖显微外科手术的牙医。
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引用次数: 0
A blood glucose fluctuation-responsive delivery system promotes bone regeneration and the repair function of Smpd3-reprogrammed BMSC-derived exosomes 血糖波动响应递送系统促进骨再生和smpd3重编程bmsc衍生外泌体的修复功能
IF 14.9 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2024-12-01 DOI: 10.1038/s41368-024-00328-6
Lingxiao Wang, Haoqing Yang, Chen Zhang, Yue Zhang, Yilin He, Yang Liu, Pan Ma, Jun Li, Zhipeng Fan

Blood glucose fluctuation leads to poor bone defect repair in patients with type 2 diabetes (T2DM). Strategies to safely and efficiently improve the bone regeneration disorder caused by blood glucose fluctuation are still a challenge. Neutral sphingophospholipase 2 (Smpd3) is downregulated in jawbone-derived bone marrow mesenchymal stem cells (BMSCs) from T2DM patients. Here, we investigated the effect of Smpd3 on the osteogenic differentiation of BMSCs and utilized exosomes from stem cells overexpressing Smpd3 as the main treatment based on the glucose responsiveness of phenylboronic acid-based polyvinyl alcohol crosslinkers and the protease degradability of gelatin nanoparticles. The combined loading of Smpd3-overexpressing stem cell-derived exosomes (Exos-Smpd3) and nanosilver ions (Ns) to construct a hydrogel delivery system (Exos-Smpd3@Ns) promoted osteogenesis and differentiation of BMSCs in a glucose-fluctuating environment, ectopic osteogenesis of BMSCs in a glucose-fluctuating environment and jawbone regeneration of diabetic dogs in vitro. Mechanistically, Smpd3 promoted the osteogenesis and differentiation of jawbone-derived BMSCs by activating autophagy in the jawbone and inhibiting macrophage polarization and oxidative stress caused by blood glucose fluctuations. These results reveal the role and mechanism of Smpd3 and the Smpd3 overexpression exosome delivery system in promoting BMSC function and bone regeneration under blood glucose fluctuations, providing a theoretical basis and candidate methods for the treatment of bone defects in T2DM patients.

血糖波动导致2型糖尿病(T2DM)患者骨缺损修复不良。如何安全有效地改善由血糖波动引起的骨再生障碍仍然是一个挑战。中性鞘磷脂酶2 (Smpd3)在T2DM患者颌骨源性骨髓间充质干细胞(BMSCs)中下调。在这里,我们研究了Smpd3对骨髓间充质干细胞成骨分化的影响,并利用过表达Smpd3的干细胞外泌体作为主要处理方法,基于苯硼酸基聚乙烯醇交联剂的葡萄糖反应性和明胶纳米颗粒的蛋白酶降解性。将过表达smpd3的干细胞衍生外泌体(Exos-Smpd3)和纳米银离子(Ns)联合负载构建水凝胶递送系统(Exos-Smpd3@Ns),可促进葡萄糖波动环境下骨髓间充质干细胞的成骨和分化、葡萄糖波动环境下骨髓间充质干细胞的异位成骨以及糖尿病犬的体外颌骨再生。机制上,Smpd3通过激活颌骨自噬,抑制血糖波动引起的巨噬细胞极化和氧化应激,促进颌骨源性骨髓间质干细胞成骨分化。这些结果揭示了Smpd3及Smpd3过表达外泌体递送系统在血糖波动下促进BMSC功能和骨再生中的作用和机制,为T2DM患者骨缺损的治疗提供了理论基础和候选方法。
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引用次数: 0
Correction: An unexpected role of Nogo-A as regulator of tooth enamel formation. 更正:Nogo-A 作为牙釉质形成调节剂的意外作用。
IF 12.7 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2024-11-08 DOI: 10.1038/s41368-024-00330-y
Pierfrancesco Pagella, Chai Foong Lai, Laurence Pirenne, Claudio Cantù, Martin E Schwab, Thimios A Mitsiadis
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引用次数: 0
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