Smoking and tetramer tryptase accelerate intervertebral disc degeneration by inducing METTL14-mediated DIXDC1 m6 modification

• DOI: 10.1016/j.ymthe.2023.06.010
• Publication Date: 2023-06-19T20:04:13Z
• Authors: Ji Tu; Wentian Li; Philip M. Hansbro; Qi Yan; Xupeng Bai; Chantal Donovan; Richard Y. Kim; Izabela Galvao; Abhirup Das; Cao Yang; Jun Zou; Ashish Diwan
• Keywords: Intervertebral Disc; Degeneration (medical)

Although cigarette smoking (CS) and low back pain (LBP) are common worldwide, their correlations the mechanisms of action remain unclear. We have shown that excessive activation mast cells (MCs) proteases play key roles in CS-associated diseases, like asthma, chronic obstructive pulmonary disease (COPD), blood coagulation, lung cancer. Previous studies also MCs induce degenerative musculoskeletal disease. By using a custom-designed smoke-exposure mouse system, we demonstrated CS results intervertebral disc (IVD) degeneration release MC-restricted tetramer tryptases (TTs) IVDs. TTs were found to regulate expression methyltransferase 14 (METTL14) at epigenetic level by inducing N6-methyladenosine (m