Zebrafish Models of Arthritis and Their Applications in Traditional Chinese Medicine Screening: Advances and Perspectives

Jialu Luo; Min Gao; Xianglu Li; Xiang Guo; Huilian Huang; Xiaoqiang Hou; Zhigang Mei; Zhitao Feng;

HIGHLIGHT

In this review, we searched CNKI and PubMed up to July 30, 2026 using combinations of "zebrafish", "arthritis", "osteoarthritis", "rheumatoid arthritis", "gouty arthritis", "infectious arthritis", "traditional Chinese medicine", and "natural products".

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ABSTRACT

The zebrafish is a widely utilized model organism in medical research because of its high reproductive capacity, rapid development, transparent embryos, genetic tractability, and similarity to humans in skeletal development. In this review, we searched CNKI and PubMed up to July 30, 2026 using combinations of "zebrafish", "arthritis", "osteoarthritis", "rheumatoid arthritis", "gouty arthritis", "infectious arthritis", "traditional Chinese medicine", and "natural products". Both Chinese and English articles were considered. A total of 67 articles were initially retrieved. After manual screening against the inclusion criteria, the most relevant studies were selected for this review. Studies were reviewed when they described zebrafish arthritis-related models, inflammatory or skeletal phenotypes, or TCM/natural product screening. Current research has applied zebrafish models mainly to osteoarthritis (OA) and rheumatoid arthritis (RA), while infectious and gouty arthritis models remain less developed. These models help elucidate pathogenic genes associated with OA, evaluate induced OA-like pathology, explore immune and vascular mechanisms in RA, simulate acute gout-related innate inflammation, and investigate host-pathogen responses relevant to infectious arthritis. Compared with previous reviews, this review specifically addresses the application of zebrafish arthritis models in traditional Chinese medicine (TCM) screening, with emphasis on model classification and current limitations. TCM compounds and formulas can be evaluated in zebrafish through whole-organism phenotypes including inflammatory-cell recruitment, angiogenesis, toxicity, and drug-response patterns. These findings demonstrate anti-angiogenic activities that may be relevant to arthritis, but they do not establish therapeutic efficacy against arthritis itself. Future studies should further refine zebrafish models for specific arthritis types, report strain background and dose more consistently, and validate larval screening results in adult zebrafish or mammalian models when possible, as zebrafish are complementary screening models that cannot fully reproduce all aspects of adult human arthritis.

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