Joint inflammation alters gene and protein expression and leads to atrophy in the tibialis anterior muscle in rats.

Objective: The aim of this study was to evaluate the effect of tibiotarsal joint inflammation in rat tibialis anterior muscle through muscle fiber cross-sectional area (CSA) and gene expression (atrogin-1, muscle ring finger-1 [MuRF1], myogenic differentiation-1 [MyoD], p38 mitogen-activated protein kinase [p38MAPK], nuclear factor kappa B-dependent [NFκB], tumor necrosis factor-alpha [TNF-α]).

Design: Wistar rats were randomly divided into three periods (2, 7, and 15 days) and assigned into four groups within each experimental period: control, sham, inflammation, and immobilization. Real-time polymerase chain reaction, Western blot, immunofluorescence, and muscle fiber CSA analyses were performed.

Results: At 2 days, the inflammation group increased atrogin-1, MuRF1, and myostatin and reduced MyoD expression. At 7 days, the inflammation group increased atrogin-1, MuRF1, NFκB, p38MAPK, MyoD, myostatin, and TNF-α expression and TNF-α protein and reduced muscle fiber CSA. At 15 days, gene and protein expression in the inflammation group returned to basal levels, and CSA values were similar to those in control and sham groups. The immobilization groups have a similar pattern in all experimental periods, with increased atrogin-1, MuRF1, NFκB, and TNF-α gene expression and reduced muscle fiber CSA. The sham group had increased myostatin and atrogin-1 expression at 2 days and increased MyoD and myostatin expression at 7 days.

Conclusions: Joint inflammation stimulated the expression of muscle factors related to atrophy, growth, differentiation, and mass regulation followed by muscle atrophy.