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Background <p>Osteoarthritis (OA) is a whole-joint degenerative disease characterized by chronic inflammation, cartilage matrix degradation, subchondral bone remodeling, pain, and progressive functional impairment. Galectin-4 (Gal-4), a member of the galectin family, has been reported to be upregulated in osteoarthritic tissues; however, its pathophysiological relevance in OA progression remains incompletely understood.</p> Methods <p>A monosodium iodoacetate (MIA)-induced rat model of OA was established to investigate the association between Gal-4 and inflammatory activation in vivo. Pain-related behaviors were assessed using Lequesne MG scoring, paw withdrawal mechanical threshold (PWMT), and body weight monitoring. Histological alterations in articular cartilage were evaluated using hematoxylin and eosin staining, Safranin O/Fast Green staining, Mankin histological scoring, and immunohistochemistry. Inflammatory mediators and cartilage metabolism-related markers were analyzed using real-time quantitative PCR and enzyme-linked immunosorbent assay. To further explore the involvement of inflammatory pathways, the TNF-α inhibitor adalimumab was administered in Gal-4–treated OA rats. In addition, IL-1β-stimulated SW1353 cells were used to evaluate Gal-4-associated inflammatory and matrix-catabolic responses in vitro.</p> Results <p>Gal-4 administration was associated with aggravated OA-related phenotypes, including increased pain-related behavioral abnormalities, reduced mechanical pain threshold, and more pronounced structural alterations in cartilage-containing knee joint regions. Safranin O/Fast Green staining further showed reduced and uneven Safranin O-positive cartilage matrix following Gal-4 administration, indicating impaired proteoglycan preservation. These histological changes were accompanied by increased expression of inflammatory mediators and cartilage catabolic markers, together with reduced expression of cartilage anabolic markers. Mankin scores differed significantly overall among the four experimental groups and followed the same directional pattern as the qualitative histological findings, although adjusted pairwise comparisons did not reach statistical significance. Pharmacological inhibition of TNF-α partially attenuated Gal-4–associated behavioral abnormalities, cartilage matrix alterations, and inflammatory factor expression. In vitro, Gal-4 further enhanced IL-1β-induced expression of MMP13, ADAMTS-5, TNF-α, and IL-6, reduced ACAN expression, and increased TNFR1 expression and NF-κB p65 phosphorylation in SW1353 cells. TNF-α inhibition attenuated these Gal-4-associated inflammatory and matrix-catabolic responses.</p> Conclusion <p>The combined in vivo and in vitro findings suggest that Gal-4 is associated with inflammatory activation, cartilage matrix deterioration, and matrix-catabolic remodeling in experimental OA. TNF-α/NF-κB-related signaling may contribute to these Gal-4-associated inflammatory and catabolic responses. These findings support Gal-4 as a potential pathological mediator of inflammatory and cartilage-degenerative changes in OA.</p>

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Galectin-4 is associated with inflammatory activation involving TNF-α signaling in experimental osteoarthritis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月3日

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  • Zhengxue Zhang,
  • Zhouyang Lei,
  • Quan Wang,
  • Wei Wen,
  • Meifeng Li,
  • Chunji Zhu

摘要

Background

Osteoarthritis (OA) is a whole-joint degenerative disease characterized by chronic inflammation, cartilage matrix degradation, subchondral bone remodeling, pain, and progressive functional impairment. Galectin-4 (Gal-4), a member of the galectin family, has been reported to be upregulated in osteoarthritic tissues; however, its pathophysiological relevance in OA progression remains incompletely understood.

Methods

A monosodium iodoacetate (MIA)-induced rat model of OA was established to investigate the association between Gal-4 and inflammatory activation in vivo. Pain-related behaviors were assessed using Lequesne MG scoring, paw withdrawal mechanical threshold (PWMT), and body weight monitoring. Histological alterations in articular cartilage were evaluated using hematoxylin and eosin staining, Safranin O/Fast Green staining, Mankin histological scoring, and immunohistochemistry. Inflammatory mediators and cartilage metabolism-related markers were analyzed using real-time quantitative PCR and enzyme-linked immunosorbent assay. To further explore the involvement of inflammatory pathways, the TNF-α inhibitor adalimumab was administered in Gal-4–treated OA rats. In addition, IL-1β-stimulated SW1353 cells were used to evaluate Gal-4-associated inflammatory and matrix-catabolic responses in vitro.

Results

Gal-4 administration was associated with aggravated OA-related phenotypes, including increased pain-related behavioral abnormalities, reduced mechanical pain threshold, and more pronounced structural alterations in cartilage-containing knee joint regions. Safranin O/Fast Green staining further showed reduced and uneven Safranin O-positive cartilage matrix following Gal-4 administration, indicating impaired proteoglycan preservation. These histological changes were accompanied by increased expression of inflammatory mediators and cartilage catabolic markers, together with reduced expression of cartilage anabolic markers. Mankin scores differed significantly overall among the four experimental groups and followed the same directional pattern as the qualitative histological findings, although adjusted pairwise comparisons did not reach statistical significance. Pharmacological inhibition of TNF-α partially attenuated Gal-4–associated behavioral abnormalities, cartilage matrix alterations, and inflammatory factor expression. In vitro, Gal-4 further enhanced IL-1β-induced expression of MMP13, ADAMTS-5, TNF-α, and IL-6, reduced ACAN expression, and increased TNFR1 expression and NF-κB p65 phosphorylation in SW1353 cells. TNF-α inhibition attenuated these Gal-4-associated inflammatory and matrix-catabolic responses.

Conclusion

The combined in vivo and in vitro findings suggest that Gal-4 is associated with inflammatory activation, cartilage matrix deterioration, and matrix-catabolic remodeling in experimental OA. TNF-α/NF-κB-related signaling may contribute to these Gal-4-associated inflammatory and catabolic responses. These findings support Gal-4 as a potential pathological mediator of inflammatory and cartilage-degenerative changes in OA.