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Theranostics 2024; 14(1):265-282. doi:10.7150/thno.90940 This issue Cite

Review

Lymphatic vessels: roles and potential therapeutic intervention in rheumatoid arthritis and osteoarthritis

Siru Zhou^1,2#, Guangyu Zhao^3,4#, Ran Chen^1,2#, Yang Li¹, Junlan Huang², Liang Kuang², Dali Zhang^2,5, Zhijun Li⁴, Haofeng Xu⁴, Wei Xiang⁴, Yangli Xie^2✉, Lin Chen^2✉, Zhenhong Ni^4✉

1. War Trauma Medical Center, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical Center, Daping Hospital, Army Medical University, Chongqing, 40038, People's Republic of China.
2. Department of Wound Repair and Rehabilitation Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical Center, Daping Hospital, Army Medical University, Chongqing, 40038, People's Republic of China.
3. Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.
4. Rehabilitation Medicine Department, Army Medical Center, Daping Hospital, Army Medical University, Chongqing 400038, People's Republic of China.
5. The Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110015, People's Republic of China.
#These authors contributed equally to this work.

✉ Corresponding authors: xieyangli841015com; linchen70com; nizhenhong1986com.

Abstract

Lymphatic vessel networks are a main part of the vertebrate cardiovascular system, which participate in various physiological and pathological processes via regulation of fluid transport and immunosurveillance. Targeting lymphatic vessels has become a potent strategy for treating various human diseases. The presence of varying degrees of inflammation in joints of rheumatoid arthritis (RA) and osteoarthritis (OA), characterized by heightened infiltration of inflammatory cells, increased levels of inflammatory factors, and activation of inflammatory signaling pathways, significantly contributes to the disruption of cartilage and bone homeostasis in arthritic conditions. Increasing evidence has demonstrated the pivotal role of lymphatic vessels in maintaining joint homeostasis, with their pathological alterations closely associated with the initiation and progression of inflammatory joint diseases. In this review, we provide a comprehensive overview of the evolving knowledge regarding the structural and functional aspects of lymphatic vessels in the pathogenesis of RA and OA. In addition, we summarized the potential regulatory mechanisms underlying the modulation of lymphatic function in maintaining joint homeostasis during inflammatory conditions, and further discuss the distinctions between RA and OA. Moreover, we describe therapeutic strategies for inflammatory arthritis based on lymphatic vessels, including the promotion of lymphangiogenesis, restoration of proper lymphatic vessel function through anti-inflammatory approaches, enhancement of lymphatic contractility and drainage, and alleviation of congestion within the lymphatic system through the elimination of inflammatory cells. At last, we envisage potential research perspectives and strategies to target lymphatic vessels in treating these inflammatory joint diseases.

Keywords: Rheumatoid arthritis, Osteoarthritis, Inflammatory arthritis, Lymphatic vessels and Drainage function

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