STUDY DESIGN: This study investigated the expression of 2 types of ADAMTS in human intervertebral cartilage endplate (CEP) and related mechanisms concerning tumor necrosis factor α (TNF-α)-induced nuclear factor κB signaling pathway. OBJECTIVE: To determine which type of ADAMTS is more strongly expressed and the role of TNF-α in CEP. SUMMARY OF BACKGROUND DATA: ADAMTS-4 and ADAMTS-5 were proven to be essential in the degeneration of articular cartilage and intervertebral disc. CEP is an important structure adjacent to the disc. However, the activities of ADAMTS in CEP are unclear. METHODS: CEPs were obtained from subjects after spinal surgery and categorized as members of either the Modic change group or the control group. Sections of these tissues were stained with hematoxylin-eosin, safranin O, and immunohistochemistry procedures for ADAMTS-4, ADAMTS-5, and TNF-α. Transcriptional levels of aggrecan, type I collagen, type II collagen, type X collagen, ADAMTS-4, ADAMTS-5, and TNF-α were investigated by quantitative real-time polymerase chain reaction. In addition, the effect of TNF-α on ADAMTS-5 and its potential mechanisms are investigated in cultured bovine endplate chondrocytes in vitro. RESULTS: Our data demonstrated that the degenerative changes associated with the expression of extracellular matrix proteins were correlated with increased levels of ADAMTS-5, but not ADAMTS-4, in the CEP of patients with Modic changes. The expression levels of TNF-α in the Modic change group were significantly increased, which was correlated with the enhanced expression of ADAMTS-5. Additional in vitro investigation confirmed that TNF-α could upregulate the expression of ADAMTS-5 by activating nuclear factor κB pathway in cultured bovine endplate chondrocytes. CONCLUSION: We conclude that the upregulation of TNF-α and ADAMTS-5, but not ADAMTS-4, may play an important role in degenerative CEP-induced low back pain. LEVEL OF EVIDENCE: N/A.
STUDY DESIGN: This study investigated the expression of 2 types of ADAMTS in humanintervertebral cartilage endplate (CEP) and related mechanisms concerning tumor necrosis factor α (TNF-α)-induced nuclear factor κB signaling pathway. OBJECTIVE: To determine which type of ADAMTS is more strongly expressed and the role of TNF-α in CEP. SUMMARY OF BACKGROUND DATA: ADAMTS-4 and ADAMTS-5 were proven to be essential in the degeneration of articular cartilage and intervertebral disc. CEP is an important structure adjacent to the disc. However, the activities of ADAMTS in CEP are unclear. METHODS: CEPs were obtained from subjects after spinal surgery and categorized as members of either the Modic change group or the control group. Sections of these tissues were stained with hematoxylin-eosin, safranin O, and immunohistochemistry procedures for ADAMTS-4, ADAMTS-5, and TNF-α. Transcriptional levels of aggrecan, type I collagen, type II collagen, type X collagen, ADAMTS-4, ADAMTS-5, and TNF-α were investigated by quantitative real-time polymerase chain reaction. In addition, the effect of TNF-α on ADAMTS-5 and its potential mechanisms are investigated in cultured bovine endplate chondrocytes in vitro. RESULTS: Our data demonstrated that the degenerative changes associated with the expression of extracellular matrix proteins were correlated with increased levels of ADAMTS-5, but not ADAMTS-4, in the CEP of patients with Modic changes. The expression levels of TNF-α in the Modic change group were significantly increased, which was correlated with the enhanced expression of ADAMTS-5. Additional in vitro investigation confirmed that TNF-α could upregulate the expression of ADAMTS-5 by activating nuclear factor κB pathway in cultured bovine endplate chondrocytes. CONCLUSION: We conclude that the upregulation of TNF-α and ADAMTS-5, but not ADAMTS-4, may play an important role in degenerative CEP-induced low back pain. LEVEL OF EVIDENCE: N/A.
Authors: Stefan Dudli; Alexander Ballatori; Anne-Christine Bay-Jensen; Zachary L McCormick; Conor W O'Neill; Sibel Demir-Deviren; Roland Krug; Irina Heggli; Astrid Juengel; Jaro Karppinen; Florian Brunner; Mazda Farshad; Oliver Distler; Jeffrey C Lotz; Aaron J Fields Journal: Int J Mol Sci Date: 2020-05-27 Impact factor: 6.208