Targeting l-arginine-activated signals might provide new clues for the treatment of temporomandibular joint osteoarthritis

Abstract

TMJOA as a progressive degenerative disease of the TMJ, is featured as enhanced inflammation, chondrocyte apoptosis, ECM degradation and subchondral bone remodeling, resulting in local pain and functional impairment that further reduces patients’ quality of life. However, its etiology is ambiguous, leading to no consensus regarding the most effective treatment for patients with TMJOA. L-arg is a conditionally essential amino acid that participates in regulating inflammation, ECM orchestration, cellular growth and proliferation, but the role and mechanism of L-arg in TMJOA remain unclear. L-arg exerts different functions in contexts- and tissue microenvironments-dependent manner. For example, excess L-arg induces acute pancreatitis via the JAK2/STAT3 pathway, the iNOS/NO pathway and the HMGB1/TLR4/NF-κB pathway; Arg-Ⅱ in advanced atherosclerosis impairs endothelial autophagy through regulation of mTOR signaling. Interestingly, these signaling pathways are tightly involved in the reported pathological process of TMJOA. We here unexpectedly found that L-arg is significantly elevated in the plasma of TMD patients using mass spectrometry. Thus, through literature review and analysis, we proposed that the upregulation of L-arg activated iNOS/NO pathway, Arg-Ⅱ pathway, mTOR pathway and NF-κB pathway to prompt TMJOA development. Related pathway inhibitors could be an alternative treatment strategy for TMJOA.