Fibroblast growth factor 2 in the hotbed of rheumatoid arthritis pathogenesis

Fibroblast growth factor 2 (FGF2) is a multifunctional protein that functions as a potent growth factor and plays a crucial role under normal physiological and pathological conditions. Idealized as a key growth factor, FGF2 plays multiple roles as a 'mitogenic, angiogenic, and neurotrophic factor' while also influencing M1 macrophage polarization. The far-stretching implications of FGF2 have propelled its investigation in rheumatoid arthritis (RA), suggesting its role as a profibrotic player. Herein, we delve further into this subject, trying to uncover the signaling perspectives of FGF2, which is central to RA. Moreover, we explored the sophisticated activation of FGF2 to trigger inflammatory immune responses, skewed metabolic paradigms, and altered structural modalities in rheumatoid arthritis. FGF2 can skew immune responses, induce autoimmune inflammation, and drive disease progression. As we engage and deliberate further in detail, we draw parallels of key findings that could hold prospective implications for the exacerbation of this autoimmune joint disease. Furthermore, we elaborated on different combat strategies aimed at underwhelming FGF2 activation to enable RA resolution. Thus, understanding the critical consequences of FGF2 overactivation and its perplexing capabilities in health and disease could lead to promising outcomes in RA treatment.