Expression of ANGPTL4 in Nucleus Pulposus Tissues Is Associated with Intervertebral Disc Degeneration

Abstract

Objective. Angiopoietin-like protein 4 (ANGPTL4), encoding a glycosylated secreted protein, has been reported to be closely related to many kinds of diseases, including diabetes, tumor, and some musculoskeletal pathologies, such as rheumatoid arthritis, osteoarthritis, and osteoporosis. The aim of the current study is to investigate the role of ANGPTL4 in intervertebral disc degeneration and analyze the association of ANGPTL4 expression with Pfirrmann grades. Methods. A total of 162 nucleus pulposus tissues were collected from lumbar intervertebral disc herniation patients undergoing interforaminal endoscopic surgery. Real-time quantitative PCR and western blot were performed to determine the mRNA and protein expression of ANGPTL4 in nucleus pulposus samples. Statistical analysis was performed to analyze the association of ANGPTL4 expression with Pfirrmann grades. Results. Based on the clinical data of 162 patients, results showed that Pfirrmann grades were significantly associated with patients’ age ( r = 0.162 , P = 0.047 ) and were not significantly associated with patients’ gender ( P > 0.05 ). RT-qPCR and western blot results showed that the mRNA ( r = 0.287 , P < 0.05 ) and protein ( r = 0.356 , P < 0.05 ) expressions of ANGPTL4 were both closely associated with Pfirrmann grades. The expression of ANGPTL4 was remarkably increased in the groups of high IVDD Pfirrmann grades. Conclusion. The results demonstrated that ANGPTL4 expression was positively associated with the Pfirrmann grades and the severity of intervertebral disc degeneration. ANGPTL4 may be served as a candidate biomarker for intervertebral disc degeneration.

Monocytic fibrocyte-like cell enrichment and myofibroblastic adaptation causes nucleus pulposus fibrosis and associates with disc degeneration severity

“…26 genes enriched in the Fib-cNP were related to matrix organization. Two degeneration-featured genes, HTRA1 25 and ANGPTL4 26 were distinctly expressed in the NPC-fibrocytes ( Fig. 2g ).…”

“…Furthermore, the NPCenriched disc fibrocytes express HTRA1 and ANGPTL4. HTRA1 is a proteolytic enzyme for degrading the matrix either on its own 59 or by upregulating ADAMTS-5 25 or MMPs, whereas expression of ANGPTL4 is positively associated with IDD severity 26 . Their regulatory role in the fibrocytes and NP fibrosis worths to be investigated.…”

“…Furthermore, the NPC-enriched disc fibrocytes express HTRA1 and ANGPTL4 . HTRA1 is a proteolytic enzyme for degrading the matrix either on its own 62 or by upregulating ADAMTS-5 25 or MMPs, whereas expression of ANGPTL4 is positively associated with IDD severity 26 . Notably, our data suggest that ANGPTL4 is a major mediator of the intercellular communication between the disc fibrocytes and the CyclingNP, RegNP and FibroNP subpopulations.…”

Roles of organokines in intervertebral disc homeostasis and degeneration

“…However, their roles in regulating disc homeostasis are poorly understood. Recent research illustrated the correlation between the upregulation of ANGPTL4/8 and the severity of disc degeneration ( 160 , 161 ). Mechanistically, ANGPTL4/8 appears to promote matrix degradation and the production of inflammatory cytokines like TNF-α through the activation of the NF-κB signaling pathway ( 161 , 162 ).…”

Sugar-coated bullets: Unveiling the enigmatic mystery ‘sweet arsenal’ in osteoarthritis

“…ANGPTL4, as elucidated by Yang et al, emerges as another crucial player, enhanced in arthritis, potentially impacting conditions like RA, OA, or osteoporosis, emphasizing the multifaceted impact of glycosylated proteins in disease progression [ 153 ]. Tardio et al's findings on increased O-glycosylation mediating certain differentiation markers in OA shed light on the mechanism involving O-GlcNAc addition to various proteins [ 154 ].…”