Knee osteoarthritis induces atrophy and neuromuscular junction remodeling in the quadriceps and tibialis anterior muscles of rats
SCIENTIFIC REPORTS
Authors: Cunha, Jonathan Emanuel; Barbosa, Germanna Medeiros; Tome de Souza Castro, Paula Aiello; Ferreira Luiz, Beatriz Leite; Arcari Silva, Andreza Cristine; Russo, Thiago Luiz; Vasilceac, Fernando Augusto; Cunha, Thiago Mattar; Cunha, Fernando Queiroz; Salvini, Tania Fatima
Abstract
Knee osteoarthritis (KOA) is associated with muscle weakness, but it is unclear which structures are involved in the muscle changes. This study assessed morphological alterations and the expression of genes and proteins linked to muscular atrophy and neuromuscular junctions (NMJs) in KOA, induced by anterior cruciate ligament transection (ACLT) in rats. Two groups of rats were assessed: control (without intervention) and KOA (ACLT surgery in the right knee). After 8 weeks, quadriceps, tibialis anterior (TA) and gastrocnemius muscles were analyzed (area of muscle fibers, NMJ, gene and protein expression). KOA group showed atrophy in quadriceps (15.7%) and TA (33%), with an increase in atrogin-1 and muscle RING-finger protein-1 (MuRF-1). KOA group showed quadriceps NMJ remodeling (reduction area and perimeter) and decrease in NMJ diameter in TA muscle. The expression of nicotinic acetylcholine receptor (nAChR) gamma-nAChR increased and that of alpha-nAChR and muscle specific tyrosine kinase (MuSK) declined in the quadriceps, with a decrease in epsilon-nAChR in TA. MuRF-1 protein expression increased in quadriceps and TA, with no changes in neural cell adhesion molecule (NCAM). In conclusion, ACLT-induced KOA promotes NMJ remodeling and atrophy in quadriceps and TA muscles, associated with inflammatory signs and changes in muscle gene and protein expression.
Antigen-specific immunoadsorption of MuSK autoantibodies as a treatment of MuSK-induced experimental autoimmune myasthenia gravis
JOURNAL OF NEUROIMMUNOLOGY
Authors: Lazaridis, Konstantinos; Baltatzidou, Vasiliki; Tektonidis, Nikolaos; Tzartos, Socrates J.
Abstract
Myasthenia gravis (MG) is an autoimmune disease affecting the neuromuscular junction. Approximately 9% of MG patients have autoantibodies targeting the muscle specific kinase (MuSK), and are challenging therapeutically, since they often present with more severe symptoms. A useful therapy is plasmapheresis, but it is highly non-specific. Antigen-specific immunoadsorption would only remove the pathogenic autoantibodies, minimizing the possible side effects and maximizing the benefit. We used rats with human MuSK-induced experimental autoimmune MG to perform antigen-specific immunoadsorptions, and found it very effective, resulting in a dramatic autoantibody titer decrease, while immunoadsorbed, but not mock-treated, animals showed an significant improvement of their clinical symptoms. Overall, the procedure was efficient, supporting its application for MG treatment.