Macrophages regulate the progression of osteoarthritis
Macrophages regulate the progression of osteoarthritis
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巨噬细胞调节骨关节炎的进展
DOI：
10.1016/j.joca.2020.01.007
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发表时间：
2020-05-01
影响因子：
7
通讯作者：
Bai, X.
中科院分区：
文献类型：
--
作者：
Zhang, H.;Cai, D.;Bai, X.
OA现在被公认为影响整个关节的低度炎症性疾病。除了机械负荷外，炎症（特别是滑膜炎）也是OA的重要原因。滑膜巨噬细胞作为免疫细胞，在OA的病理学和结构进展中至关重要。活化的巨噬细胞受mTOR、NF-κ B、JNK、PI 3 K/Akt和其他信号通路的调节，并在OA滑膜组织、滑液和外周血中极化为M1或M2亚型。激活状态和M1/M2比值与OA严重程度高度相关。除了自分泌相互作用外，巨噬细胞和软骨细胞之间的旁分泌相互作用通过分泌炎性细胞因子、生长因子、基质金属蛋白酶（MMPs）和金属蛋白酶组织抑制剂（TIMPs）在OA的发生和发展中起重要作用，其导致随后的软骨降解和破坏。靶向滑膜巨噬细胞的治疗可缓解疼痛，并在OA发展过程中防止滑膜炎、软骨损伤和骨赘形成。从M1到M2亚型的巨噬细胞重编程转化，比活化的巨噬细胞数量的减少更多，似乎是OA的有效治疗选择。本文综述了极化巨噬细胞对关节健康和疾病的贡献。对巨噬细胞重编程具有免疫调节作用的多功能药物可以使炎症微环境向促软骨形成的气氛倾斜，因此是治疗OA和其他免疫疾病的潜在治疗选择。(C)2020年国际骨关节炎研究学会。由爱思唯尔有限公司出版。保留所有权利。
OA is now well accepted as a low-grade inflammatory disease affecting the whole joint. In addition to mechanical loading, inflammation (particularly synovitis), contributes significantly to OA. Synovial macrophages act as immune cells and are of critical importance in the symptomology and structural progression of OA. Activated macrophages are regulated by mTOR, NF-kappa B, JNK, PI3K/Akt and other signaling pathways, and are polarized into either M1 or M2 subtypes in OA synovial tissues, synovial fluid, and peripheral blood. The activation state and the M1/M2 ratio is highly associated with OA severity. Aside from autocrine interactions, paracrine interactions between macrophages and chondrocytes play a vital role in the initiation and development of OA by secreting inflammatory cytokines, growth factors, matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs), which lead to subsequent cartilage degradation and destruction. Treatments targeting synovial macrophages relieve pain, and protect from synovitis, cartilage damage, and osteophyte formation during OA development. Macrophage reprogramming of transformation from the M1 to M2 subtype, more than a decrease in the quantity of activated macrophages, appears to be an effective treatment option for OA. This review provides a broad understanding of the contributions of polarized macrophages to joint health and disease. Multifunctional agents with immunomodulatory effects on macrophage reprogramming can skew the inflammatory microenvironment towards a pro-chondrogenic atmosphere, and are thus, potential therapeutic options for the treatment of OA and other immune diseases. (C) 2020 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.