Qinwen Ge1, Jun Ying2, Zhenyu Shi1, Qiang Mao2, Hongting Jin3, Ping-Er Wang3, Jiali Chen3, Wenhua Yuan3, Peijian Tong4, Ju Li5. 1. Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310053, China; The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, China. 2. Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310053, China; Department of Orthopaedic Surgery, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China. 3. Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310053, China. 4. Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310053, China; Department of Orthopaedic Surgery, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China. Electronic address: peijiantongzjtcm@163.com. 5. Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310053, China; Department of Orthopaedic Surgery, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China. Electronic address: dliju@aliyun.com.
Abstract
AIMS: Intervertebral Disc Degeneration (IDD) is a key factor involved in low back pain (LBP) which affects approximately 540 million individuals worldwide. Chlorogenic Acid (CGA), a natural compound, exerts anti-inflammatory property in several diseases. Here, we aim to investigate the biological effect of CGA on IDD and explore the underlying mechanism. MATERIALS AND METHODS: Lumbar spine instability (LSI) model in mice was utilized to mimic process of IDD. The effects of CGA in response to LSI were evaluated by luminescent imaging, micro-CT, histomorphology, and immunohistochemistry in vivo. Besides, the cytotoxicity of CGA on chondrocytes was detected by cell counting kit-8 (CCK-8) and the biological effects were assessed by polymerase chain reaction (PCR) in vitro. KEY FINDINGS: We found that CGA treatment dramatically suppressed the NF-κB activity in LSI mice. Moreover, administration of CGA mitigated cartilaginous endplate degeneration and postponed IDD development accompanying a decrease of inflammatory and catabolic mediators. Specifically, CGA ameliorated endplate degeneration might be related to its protective effects against endplate chondrocytes apoptosis and trans-differentiation. We further elucidated that CGA exerted these biological effects mainly by repressing NF-κB signaling in cartilage endplate. SIGNIFICANCE: Our study has illustrated, for the first time, the curative effects as well as the latent mechanism of CGA in IDD and our results suggested that CGA administration might be used as an alternative therapy for IDD.
AIMS: Intervertebral Disc Degeneration (IDD) is a key factor involved in low back pain (LBP) which affects approximately 540 million individuals worldwide. Chlorogenic Acid (CGA), a natural compound, exerts anti-inflammatory property in several diseases. Here, we aim to investigate the biological effect of CGA on IDD and explore the underlying mechanism. MATERIALS AND METHODS: Lumbar spine instability (LSI) model in mice was utilized to mimic process of IDD. The effects of CGA in response to LSI were evaluated by luminescent imaging, micro-CT, histomorphology, and immunohistochemistry in vivo. Besides, the cytotoxicity of CGA on chondrocytes was detected by cell counting kit-8 (CCK-8) and the biological effects were assessed by polymerase chain reaction (PCR) in vitro. KEY FINDINGS: We found that CGA treatment dramatically suppressed the NF-κB activity in LSI mice. Moreover, administration of CGA mitigated cartilaginous endplate degeneration and postponed IDD development accompanying a decrease of inflammatory and catabolic mediators. Specifically, CGA ameliorated endplate degeneration might be related to its protective effects against endplate chondrocytes apoptosis and trans-differentiation. We further elucidated that CGA exerted these biological effects mainly by repressing NF-κB signaling in cartilage endplate. SIGNIFICANCE: Our study has illustrated, for the first time, the curative effects as well as the latent mechanism of CGA in IDD and our results suggested that CGA administration might be used as an alternative therapy for IDD.