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Treatment of Periodontal Inflammation in Diabetic Rats with Injectable IL-1Ra Thermosensitive Hydrogel 注射IL-1Ra热敏水凝胶治疗糖尿病大鼠牙周炎症
Pub Date : 1900-01-01 DOI: 10.2139/ssrn.3943648
Yue Liu, Chang Liu, Chang Wang, Qian Zhang, Xingyuan Qu, Chen Liang, Lei Wang
Periodontitis is a chronic inflammatory disease in which dental plaque plays a key role. Hyperglycemia can promote inflammatory cells to secrete various inflammatory factors, causing the destruction of periodontal tissues and leading to the sustained development of periodontitis and prolonged and unhealed periodontal tissues. IL-1β is an important prophase inflammatory factor, which participates in the pathophysiological process of periodontitis. Interleukin 1 receptor antagonist (IL-1Ra), a natural inhibitor of IL-1, can also reduce the levels of other cytokines, including TNF-α and IL-6, and the balance between IL-1Ra and IL-1β is one of the primary factors affecting chronic periodontitis(CP). In this experiment, a temperature-sensitive hydrogel loaded with IL-1Ra was prepared and characterized, and its anti-inflammatory properties were evaluated. The hydrogel could be injected locally, and the results showed that it had good morphology, was nontoxic both in vivo and in vitro, and could realize sustained drug release. Histological evaluation and micro-computed tomography (micro-CT) showed that IL-1Ra-loaded thermosensitive hydrogel could effectively inhibit periodontal inflammation in diabetic rats, and played a significant role in relieving hyperglycemia. Therefore, IL-1Ra-loaded thermosensitive hydrogel may be an effective method to treat periodontitis with diabetes. Funding: This work was supported by grants from the Science and Technology Research Project of Education Department of Jilin Province(JJKH20211218KJ),"13th Five-Year plan" science and technology project of Education Department of Jilin Province(JJKH20201115KJ). Declaration of Interests: The authors report no declarations of interest. Ethics Approval Statement: This experiment was approved by the Ethics Committee of the Hospital of Stomatology, Jilin University,China, and all animal experiments followed the National Institute of Health (NIH) guidelines on laboratory animal care and use (ARRIVE guidelines).
牙周炎是一种慢性炎症性疾病,其中牙菌斑起着关键作用。高血糖可促进炎症细胞分泌各种炎症因子,造成牙周组织的破坏,导致牙周炎持续发展,牙周组织长期不愈合。IL-1β是一种重要的前期炎症因子,参与牙周炎的病理生理过程。白细胞介素1受体拮抗剂(IL-1Ra)是一种天然的IL-1抑制剂,也可以降低其他细胞因子的水平,包括TNF-α和IL-6, IL-1Ra和IL-1β之间的平衡是影响慢性牙周炎(CP)的主要因素之一。本实验制备并表征了一种负载IL-1Ra的温度敏感水凝胶,并对其抗炎性能进行了评价。结果表明,该水凝胶具有良好的形态,体内外均无毒,并能实现药物的持续释放。组织学评价和显微ct (micro-computed tomography, micro-CT)显示,负载il - 1ra的热敏水凝胶能有效抑制糖尿病大鼠牙周炎症,具有明显的缓解高血糖作用。因此,il - 1ra负载的热敏水凝胶可能是治疗牙周炎合并糖尿病的有效方法。基金资助:吉林省教育厅科技攻关项目(JJKH20211218KJ)、吉林省教育厅“十三五”科技攻关项目(JJKH20201115KJ)资助。利益声明:作者没有利益声明。伦理批准声明:本实验经中国吉林大学口腔医院伦理委员会批准,所有动物实验均遵循美国国立卫生研究院(NIH)实验动物护理和使用指南(ARRIVE指南)。
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引用次数: 0
The Immune Microenvironment in Cartilage Injury, Repair and Regeneration 软骨损伤、修复和再生中的免疫微环境
Pub Date : 1900-01-01 DOI: 10.2139/ssrn.3906848
Muzhe Li, Han Yin, Zineng Yan, Huiyun Li, Jiang Wu, Yue Wang, Fu Wei, Guangzhao Tian, Chao Ning, Haojiang Li, Cangjian Gao, Liwei Fu, Shuangpeng Jiang, Mingxue Chen, X. Sui, Shuyun Liu, Zhiwei Chen, Q. Guo
Since articular cartilage lacks blood vessels, nerves, and lymph tissue, its ability to repair itself is limited. Once damaged, it can lead to joint swelling and pain, accelerating the progression of osteoarthritis. Complete regeneration of hyaline cartilage with good mechanical properties remains an elusive goal, despite the many technologies available today. The inflammatory milieu created by cartilage damage is critical for chondrocyte death and hypertrophy, extracellular matrix breakdown, ectopic bone formation, and the progression of cartilage injury to osteoarthritis. In the inflammatory microenvironment, MSCs undergo aberrant differentiation, and chondrocytes begin to convert or dedifferentiate into cells with a fibroblast phenotype, resulting in fibrocartilage with poor mechanical qualities. All of these suggest that inflammatory problems may be a major stumbling block to cartilage repair. To produce a milieu conducive to cartilage regeneration, multi-dimensional management of the joint inflammatory microenvironment in place and time is required. Therefore, it is of great significance to elucidate the immune microenvironment of cartilage repair and regeneration after injury. This review provides a brief overview of:(1)the pathogenesis of cartilage injury(2)immune cells in cartilage injury and repair(3)effects of inflammatory cytokines on cartilage repair;(4)clinical strategies for the treatment of cartilage defects(5)strategies for targeted immunoregulation in cartilage repair and regeneration.
由于关节软骨缺乏血管、神经和淋巴组织,其自我修复能力受到限制。一旦受损,它会导致关节肿胀和疼痛,加速骨关节炎的进展。尽管今天有许多技术可用,但具有良好机械性能的透明软骨的完全再生仍然是一个难以实现的目标。软骨损伤产生的炎症环境对软骨细胞死亡和肥大、细胞外基质破坏、异位骨形成以及软骨损伤进展为骨关节炎至关重要。在炎症微环境中,间充质干细胞发生异常分化,软骨细胞开始转化或去分化为成纤维细胞表型的细胞,导致机械质量差的纤维软骨。所有这些都表明,炎症问题可能是软骨修复的主要障碍。为了产生一个有利于软骨再生的环境,需要对关节炎症微环境在地点和时间上进行多维度管理。因此,研究损伤后软骨修复与再生的免疫微环境具有重要意义。本文综述了以下方面的研究进展:(1)软骨损伤的发生机制;(2)免疫细胞在软骨损伤和修复中的作用;(3)炎症因子在软骨修复中的作用;(4)软骨缺损治疗的临床策略;(5)靶向免疫调节在软骨修复和再生中的策略。
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