Mast Cells and Their Related Gene HK-1 are Closely Associated with Discogenic Low Back Pain: A Bioinformatics and Clinical Sample Study

Abstract

Shouyu He,1,* Xiaowen Liu,2,* Shenchang Luo,1 Haidong Li,1 Jikang Min,1 Qian Shi3 1Department of Spine Surgery, First Affiliated Hospital, The First People’s Hospital of Huzhou, Huzhou University, Huzhou, 313000, People’s Republic of China; 2Department of Orthopedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, People’s Republic of China; 3Key Laboratory for Translational Medicine, First Affiliated Hospital, The First People’s Hospital of Huzhou, Huzhou University, Huzhou, 313000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qian Shi, Key Laboratory for Translational Medicine, First Affiliated Hospital, The First People’s Hospital of Huzhou, Huzhou University, Huzhou, 313000, People’s Republic of China, Email [email protected]: Low back pain (LBP) is primarily caused by intervertebral disc degeneration (IVDD). Immune cells penetrating nucleus pulposus (NP) tissues may play an important role in generating IVDD and LBP.Methods: The clinical data from 100 cases of IVDD patients was initially analyzed retrospectively. Subsequently, peripheral blood and NP tissues from 41 IVDD patients were gathered for a validated investigation. Among them, ribosome-removed-RNA sequencing (RNA-seq) was performed on 10 cases of NP tissues of specific classifications (VAS 3 and Pfirrmann 3 were used as the controls, while patients with VAS 6 and Pfirrmann 5 were used as the experimental group). Differentially expressed genes (DEGs) were identified for the subsequent bioinformatics analysis. Further methods to confirm the underlying cause of discogenic LBP included mast cell immunohistochemistry (IHC), 12 cytokine detection, Western blot (WB), and real-time polymerase chain reaction (RT-PCR).Results: Discogenic LBP and IVDD severity are strongly associated, and immunological cell infiltration has been demonstrated to be a significant factor in LBP by bioanalytical research. Tryptase-positive mast cells were found to be significantly more abundant in the VAS 6 NP tissues of IVDD patients than in the VAS 3 NP tissues. It was initially demonstrated that IVDD and LBP were significantly impacted by hemokinin-1 (HK-1), the mast cell-related gene. Furthermore, blood levels of interleukin 12 p70 (IL-12P70) are noticeably elevated and strongly correlated with HK-1, indicating that HK-1 may be involved in the regulation of mast cell activity and IL-12P70 production.Conclusion: The severity of LBP was observed to be positively correlated with the IVDD Pfirrmann grading. Further research indicates that patients with IVDD may experience persistent low back pain due to HK-1 activation of mast cells and the release of the cytokine IL12P70. This work will offer new insights into the diagnosis and treatment of discogenic LBP.Keywords: IVDD, LBP, immune cell infiltration, mast cell, HK-1

Keywords

• ivdd
• lbp
• immune cell infiltration
• mast cell
• hk-1