n-3 polyunsaturated fatty acids delay intervertebral disc degeneration by inhibiting nuclear receptor coactivator 4-mediated iron overload
Xiang Ao,
Tao Jiang,
Yuan Li,
Weiyi Lai,
Zhengnan Lian,
Liang Wang,
Minjun Huang,
Zhongmin Zhang
Affiliations
Xiang Ao
Division of Spine Surgery, Department of Orthopaedics, Nanfang Hospital of Southern Medical University, Guangzhou, Guangdong, P.R. China
Tao Jiang
Division of Spine Surgery, Department of Orthopaedics, Nanfang Hospital of Southern Medical University, Guangzhou, Guangdong, P.R. China
Yuan Li
Department of Spine Surgery, Center for Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, P.R. China; Academy of Orthopaedics·Guangdong Province, Guangzhou, Guangdong, P.R. China
Weiyi Lai
Department of Spine Surgery, Center for Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, P.R. China; Academy of Orthopaedics·Guangdong Province, Guangzhou, Guangdong, P.R. China
Zhengnan Lian
Department of Spine Surgery, Center for Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, P.R. China; Academy of Orthopaedics·Guangdong Province, Guangzhou, Guangdong, P.R. China
Liang Wang
Department of Spine Surgery, Center for Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, P.R. China; Academy of Orthopaedics·Guangdong Province, Guangzhou, Guangdong, P.R. China
Minjun Huang
Department of Spine Surgery, Center for Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, P.R. China; Academy of Orthopaedics·Guangdong Province, Guangzhou, Guangdong, P.R. China; Corresponding author
Zhongmin Zhang
Division of Spine Surgery, Department of Orthopaedics, Nanfang Hospital of Southern Medical University, Guangzhou, Guangdong, P.R. China; Corresponding author
Summary: n-3 polyunsaturated fatty acids (PUFAs) are closely related to the progression of numerous chronic inflammatory diseases, but the role of n-3 PUFAs in the intervertebral disc degeneration (IVDD) remains unclear. In this study, male C57BL/6 wildtype mice (WT group, n = 30) and fat-1 transgenic mice (TG group, n = 30) were randomly selected to construct the IVDD model. The results demonstrated that the optimized composition of PUFAs in the TG mice had a significant impact on delaying IVDD and cellular senescence of intervertebral disc (IVD). Mechanismly, n-3 PUFAs inhibited IVD senescence by alleviating NCOA4-mediated iron overload. NCOA4 overexpression promoted iron overload and weakened the pro-proliferation and anti-senescence effect of DHA on the IVD cells. Furthermore, this study futher revealed n-3 PUFAs downregulated NCOA4 expression by inactiviting the LGR5/β-catenin signaling pathway. This study provides an important theoretical basis for preventing and treating IVDD and low back pain.
