International Journal of Molecular Sciences · Oct 30, 2026
LED Photobiomodulation at 630 nm Attenuates TNF-α-Induced Senescence-Associated Responses in Association with Mitochondrial Homeostasis
By Li X, Zhang L, Wang N et al.
Chronic inflammation can accelerate the aging of joint tissues, characterized by cellular senescence, inflammatory degeneration, and disrupted tissue homeostasis. The accumulation of senescent cells and the excessive release of senescence-associated secretory phenotype (SASP) factors are accompanied by mitochondrial dysfunction, including increased oxidative stress, reduced mitochondrial membrane potential, and impaired mitochondrial quality control. Since TNF-α is a key inflammatory mediator in arthritic tissues, we used TNF-α-stimulated human fibroblast-like synoviocytes (MH7A) and chondrocytes (C28/I2), along with hTNF-α transgenic mice, to investigate whether 630 nm LED photobiomodulation therapy (PBMT) attenuates inflammatory and senescence-associated responses and whether these effects are linked to the restoration of mitochondrial homeostasis. Transcriptomic analysis, cell-based assays, and tissue immunohistochemistry were used to assess inflammatory and senescence-associated gene expression, mitochondrial features, autophagy-related proteins, and SIRT1/PGC-1α levels. PBMT reduced the TNF-α-induced expression of IL-6, IL-1β, IL-8, MMP-3, MMP-13, p16, and p21 in both cell models. Further experiments in C28/I2 cells showed that TNF-α increased reactive oxygen species (ROS) production, reduced mitochondrial membrane potential, disrupted mitochondrial ultrastructure, altered autophagy-related protein expression, and decreased SIRT1 and PGC-1α expression. These alterations were partially reversed by PBMT, accompanied by the restoration of mitochondrial homeostasis-related markers. Extending the in vitro findings, in vivo experiments using hTNF-α transgenic mice showed that PBMT enhanced the immunostaining signals of SIRT1 and PGC-1α in joint tissues. Overall, these findings indicate that PBMT attenuates TNF-α-induced inflammatory and senescence-associated responses in joint cells, which are associated with mitochondrial homeostasis, supporting further mechanistic and functional evaluation of this intervention.