Bone regeneration in inflammation with aging and cell-based immunomodulatory therapy.

IF 5 3区 医学 Q2 IMMUNOLOGY Inflammation and Regeneration Pub Date : 2023-05-25 DOI:10.1186/s41232-023-00279-1
Junichi Kushioka, Simon Kwoon-Ho Chow, Masakazu Toya, Masanori Tsubosaka, Huaishuang Shen, Qi Gao, Xueping Li, Ning Zhang, Stuart B Goodman
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引用次数: 12

Abstract

Aging of the global population increases the incidence of osteoporosis and associated fragility fractures, significantly impacting patient quality of life and healthcare costs. The acute inflammatory reaction is essential to initiate healing after injury. However, aging is associated with "inflammaging", referring to the presence of systemic low-level chronic inflammation. Chronic inflammation impairs the initiation of bone regeneration in elderly patients. This review examines current knowledge of the bone regeneration process and potential immunomodulatory therapies to facilitate bone healing in inflammaging.Aged macrophages show increased sensitivity and responsiveness to inflammatory signals. While M1 macrophages are activated during the acute inflammatory response, proper resolution of the inflammatory phase involves repolarizing pro-inflammatory M1 macrophages to an anti-inflammatory M2 phenotype associated with tissue regeneration. In aging, persistent chronic inflammation resulting from the failure of M1 to M2 repolarization leads to increased osteoclast activation and decreased osteoblast formation, thus increasing bone resorption and decreasing bone formation during healing.Inflammaging can impair the ability of stem cells to support bone regeneration and contributes to the decline in bone mass and strength that occurs with aging. Therefore, modulating inflammaging is a promising approach for improving bone health in the aging population. Mesenchymal stem cells (MSCs) possess immunomodulatory properties that may benefit bone regeneration in inflammation. Preconditioning MSCs with pro-inflammatory cytokines affects MSCs' secretory profile and osteogenic ability. MSCs cultured under hypoxic conditions show increased proliferation rates and secretion of growth factors. Resolution of inflammation via local delivery of anti-inflammatory cytokines is also a potential therapy for bone regeneration in inflammaging. Scaffolds containing anti-inflammatory cytokines, unaltered MSCs, and genetically modified MSCs can also have therapeutic potential. MSC exosomes can increase the migration of MSCs to the fracture site and enhance osteogenic differentiation and angiogenesis.In conclusion, inflammaging can impair the proper initiation of bone regeneration in the elderly. Modulating inflammaging is a promising approach for improving compromised bone healing in the aging population.

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老化和细胞免疫调节疗法在炎症中的骨再生。
全球人口老龄化增加了骨质疏松症和相关脆性骨折的发病率,显著影响了患者的生活质量和医疗保健费用。急性炎症反应是损伤后开始愈合所必需的。然而,衰老与“炎症”有关,指的是全身低水平慢性炎症的存在。慢性炎症损害老年患者骨再生的启动。本文综述了目前对骨再生过程和潜在的免疫调节疗法的了解,以促进炎症中的骨愈合。衰老的巨噬细胞对炎症信号的敏感性和反应性增加。虽然M1巨噬细胞在急性炎症反应期间被激活,但炎症期的适当解决涉及将促炎M1巨噬细胞再极化为与组织再生相关的抗炎M2表型。在衰老过程中,由于M1到M2再极化失败导致的持续慢性炎症导致破骨细胞活化增加,成骨细胞形成减少,从而增加骨吸收,减少愈合过程中的骨形成。炎症会损害干细胞支持骨骼再生的能力,并导致骨量和强度随年龄增长而下降。因此,调节炎症是改善老年人骨骼健康的一种很有前途的方法。间充质干细胞(MSCs)具有免疫调节特性,可能有利于炎症中的骨再生。用促炎细胞因子预处理MSCs会影响MSCs的分泌谱和成骨能力。在低氧条件下培养的MSCs增殖率和生长因子的分泌增加。通过局部传递抗炎细胞因子来解决炎症也是炎症中骨再生的潜在治疗方法。含有抗炎细胞因子、未改变的间充质干细胞和转基因间充质干细胞的支架也具有治疗潜力。间充质干细胞外泌体可以促进间充质干细胞向骨折部位的迁移,促进成骨分化和血管生成。总之,炎症会损害老年人骨再生的正常启动。调节炎症是一种有希望的方法,以改善受损的骨愈合在老龄化人口。
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来源期刊
CiteScore
11.10
自引率
1.20%
发文量
45
审稿时长
11 weeks
期刊介绍: Inflammation and Regeneration is the official journal of the Japanese Society of Inflammation and Regeneration (JSIR). This journal provides an open access forum which covers a wide range of scientific topics in the basic and clinical researches on inflammation and regenerative medicine. It also covers investigations of infectious diseases, including COVID-19 and other emerging infectious diseases, which involve the inflammatory responses. Inflammation and Regeneration publishes papers in the following categories: research article, note, rapid communication, case report, review and clinical drug evaluation.
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