PMID- 35528509 OWN - NLM STAT- MEDLINE DCOM- 20220510 LR - 20220716 IS - 1942-0994 (Electronic) IS - 1942-0900 (Print) IS - 1942-0994 (Linking) VI - 2022 DP - 2022 TI - Intervertebral Disc Degeneration and Low Back Pain Depends on Duration and Magnitude of Axial Compression. PG - 1045999 LID - 10.1155/2022/1045999 [doi] LID - 1045999 AB - PURPOSE: The pathological role of axial stress in intervertebral disc degeneration (IDD) is controversial, and there was no quantified study until now. Here, we tried to clarify the correlation between IDD or low back pain (LBP) and axial stress at different duration and magnitude in vitro and in vivo. METHOD: In vitro, the gene expression of aggrecan, matrix metalloproteinase-3 (MMP3), calcitonin gene-related peptide (CGRP), and substance P (SP) was measured when nucleus pulposus cells (NPCs) were compressed under gradual severity. In vivo, a measurable Ilizarov-type compression apparatus was established for single coccygeal (Co) intervertebral disc (IVD) compression of Co7-8 in mouse. Gradient stress was placed at 0.4 Mpa (mild), 0.8 Mpa (moderate), and 1.2 Mpa (severe) for three days to investigate the effect of the magnitude of axial stress. Additionally, mild compression with 3, 7, and 14 days was used to determine the effect of the duration of axial stress. Subsequently, we evaluated the severity of IDD and LBP by radiological X-ray film; histological examination with H&E staining; immunohistochemical analysis with collagen II, aggrecan, and CGRP staining; and western blot analysis with collagen II, aggrecan, MMP-3, and interleukin-1beta (IL-1beta). RESULTS: When NPCs suffered gradual increased mechanical stress, the cells exhibited gradual downregulated expression of extracellular matrix (ECM)-related gene of aggrecan, upregulated expression of IDD-related gene of MMP3, and LBP-related gene of CGRP and SP. In the meantime, with different magnitudes of axial stress, the IVD showed progressively severe IDD and LBP, with gradual narrowing intervertebral height, destruction of IVD anatomy, decreased ECM, and increased catabolic factors and proalgesic peptides. CONCLUSION: Axial compression is one of the critical pathological factors to cause IDD and LBP, and there was a strong positive correlation depended on the duration and magnitude of compression. CI - Copyright (c) 2022 Jitian Li et al. FAU - Li, Jitian AU - Li J AUID- ORCID: 0000-0001-5449-8084 AD - Henan Luoyang Orthopedic Hospital (Henan Provincial Orthopedic Hospital), Henan Provincial Orthopedic Institute, Zhengzhou 450000, China. AD - Henan University of Chinese Medicine, Zhengzhou 450046, China. FAU - Ma, Yan AU - Ma Y AD - Henan Luoyang Orthopedic Hospital (Henan Provincial Orthopedic Hospital), Henan Provincial Orthopedic Institute, Zhengzhou 450000, China. AD - Henan University of Chinese Medicine, Zhengzhou 450046, China. FAU - Jiao, Yucheng AU - Jiao Y AD - Department of Orthopeadics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China. AD - Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China. FAU - Xu, Libo AU - Xu L AD - Department of Orthopeadics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China. AD - Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China. FAU - Luo, Yage AU - Luo Y AD - Henan Luoyang Orthopedic Hospital (Henan Provincial Orthopedic Hospital), Henan Provincial Orthopedic Institute, Zhengzhou 450000, China. AD - Henan University of Chinese Medicine, Zhengzhou 450046, China. FAU - Zheng, Jiancheng AU - Zheng J AUID- ORCID: 0000-0002-8932-1876 AD - Department of Orthopeadics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China. AD - Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China. FAU - Zhang, Xingkai AU - Zhang X AUID- ORCID: 0000-0002-0621-2499 AD - Department of Orthopeadics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China. AD - Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China. FAU - Chen, Zhe AU - Chen Z AUID- ORCID: 0000-0002-9721-5301 AD - Department of Orthopeadics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China. AD - Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China. LA - eng PT - Journal Article DEP - 20220429 PL - United States TA - Oxid Med Cell Longev JT - Oxidative medicine and cellular longevity JID - 101479826 RN - 0 (Aggrecans) RN - 9007-34-5 (Collagen) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) RN - JHB2QIZ69Z (Calcitonin Gene-Related Peptide) SB - IM MH - Aggrecans/genetics MH - Animals MH - Calcitonin Gene-Related Peptide/metabolism MH - Collagen/metabolism MH - *Intervertebral Disc/metabolism MH - *Intervertebral Disc Degeneration/pathology MH - *Low Back Pain MH - Matrix Metalloproteinase 3/metabolism MH - Mice PMC - PMC9076309 COIS- The authors declare that they have no conflict of interest. EDAT- 2022/05/10 06:00 MHDA- 2022/05/11 06:00 PMCR- 2022/04/29 CRDT- 2022/05/09 03:57 PHST- 2022/02/04 00:00 [received] PHST- 2022/03/15 00:00 [revised] PHST- 2022/04/09 00:00 [accepted] PHST- 2022/05/09 03:57 [entrez] PHST- 2022/05/10 06:00 [pubmed] PHST- 2022/05/11 06:00 [medline] PHST- 2022/04/29 00:00 [pmc-release] AID - 10.1155/2022/1045999 [doi] PST - epublish SO - Oxid Med Cell Longev. 2022 Apr 29;2022:1045999. doi: 10.1155/2022/1045999. eCollection 2022.