Department of Molecular and Cellular Biochemistry, Osaka University Graduate School of Dentistry, Osaka 565-0871, Japan.
Int J Mol Sci. 2022 May 11;23(10):5365. doi: 10.3390/ijms23105365.
Inflammation is a pivotal response to a variety of stimuli, and inflammatory molecules such as cytokines have central roles in the pathogenesis of various diseases, including bone and joint diseases. Proinflammatory cytokines are mainly produced by immune cells and mediate inflammatory and innate immune responses. Additionally, proinflammatory cytokines accelerate bone resorption and cartilage destruction, resulting in the destruction of bone and joint tissues. Thus, proinflammatory cytokines are involved in regulating the pathogenesis of bone and joint diseases. Interleukin (IL)-1 is a representative inflammatory cytokine that strongly promotes bone and cartilage destruction, and elucidating the regulation of IL-1 will advance our understanding of the onset and progression of bone and joint diseases. IL-1 has two isoforms, IL-1α and IL-1β. Both isoforms signal through the same IL-1 receptor type 1, but the activation mechanisms are completely different. In particular, IL-1β is tightly regulated by protein complexes termed inflammasomes. Recent research using innovative technologies has led to a series of discoveries about inflammasomes. This review highlights the current understanding of the activation and function of the NLRP3 (NOD-like receptor family, pyrin domain-containing 3) inflammasome in bone and joint diseases.
炎症是对各种刺激的关键反应，炎症分子，如细胞因子，在各种疾病的发病机制中起着核心作用，包括骨骼和关节疾病。促炎细胞因子主要由免疫细胞产生，并介导炎症和先天免疫反应。此外，促炎细胞因子加速骨吸收和软骨破坏，导致骨和关节组织的破坏。因此，促炎细胞因子参与调节骨骼和关节疾病的发病机制。白细胞介素（IL）-1 是一种代表性的炎症细胞因子，强烈促进骨和软骨破坏，阐明 IL-1 的调节将促进我们对骨骼和关节疾病的发病和进展的理解。IL-1 有两种同工型，IL-1α 和 IL-1β。这两种同工型都通过相同的 IL-1 受体类型 1 信号转导，但激活机制完全不同。特别是，IL-1β 受到称为炎性小体的蛋白质复合物的严格调节。使用创新技术的最近研究导致了对炎性小体在骨骼和关节疾病中的激活和功能的一系列发现。这篇综述强调了目前对 NLRP3（NOD 样受体家族，含 pyrin 域 3）炎性小体在骨骼和关节疾病中的激活和功能的理解。
