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Lifestyle modifications in preclinical Rheumatoid Arthritis (RA) could delay the ongoing pathogenic immune processes and potentially prevent its onset. Physical exercise (PE) benefits RA patients; however, its impact in reducing the risk of developing RA has scarcely been studied. The objective was to describe the effects of low-intensity PE applied at the disease's preclinical phase on the joints of DBA/1 mice with collagen-induced arthritis (CIA). Twelve mice with CIA were randomly distributed into two groups: the CIA-Ex group, which undertook treadmill PE, and the CIA-NoEx, which was not exercised. The effects of PE were evaluated through clinical, histological, transcriptomics, and immunodetection analyses in the mice's hind paws. The CIA-Ex group showed lower joint inflammation and damage and a decreased expression of RA-related genes (Tnf Il2, Il10, Il12a, IL23a, and Tgfb1) and signaling pathways (Cytokines, Chemokines, JAK-STAT, MAPK, NF-kappa B, TNF, and TGF-beta). TNF-α expression was decreased by PE in the inflamed joints. Low-intensity PE in pre-arthritic CIA reduced the severity through joint down-expression of proinflammatory genes and proteins. Knowledge on the underlying mechanisms of PE in preclinical arthritis and its impact on reducing the risk of developing RA is still needed. [ABSTRACT FROM AUTHOR]

Preclinical phases of rheumatoid arthritis (RA) have been described, genetic and environmental risk factors for RA development have been identified, and several biomarkers of RA have been detected long before the clinical onset of the disease; all of which have opened the possibility for preventive interventions. Several studies are currently exploring pharmacological and non-pharmacological interventions to prevent the development of RA. We will review the evidence for prevention of RA and discuss key challenges for preventive interventions, including identification of the adequate target population, the risks of applying potentially harmful and expensive therapies to asymptomatic at-risk individuals, and the importance of taking into account the preferences of individuals at risk regarding preventive treatment options. [ABSTRACT FROM AUTHOR]