Functional self‐assembled peptide scaffold inhibits tumor necrosis factor‐alpha‐induced inflammation and apoptosis in nucleus pulposus cells by suppressing nuclear factor‐κB signaling

Abstract

Although nucleus pulposus (NP) tissue engineering has achieved tremendous success, researches still face the huge obstacles in maintaining cell survival and function. A novel functional self-assembled peptide RADA-KPSS was constructed by conjugating BMP-7 short active fragment (KPSS) to the C-terminus of RADA16-I that displays anti-inflammatory and anti-apoptosis effects. However, whether this functional self-assembled RADA-KPSS peptide can alleviate inflammation and NPC apoptosis induced by tumor necrosis factor-alpha (TNF-α) has not been studied. Therefore, we cultured NPCs treated with TNF-α for 48 h with the RADA-KPSS peptide, and compared the results to those with RADA16-I peptide. The cell apoptosis rate, inflammatory mediator secretion, expression of matrix-degrading enzymes, and extracellular matrix (ECM) protein levels were evaluated. The expression of nuclear factor-κB-p65 (NF-κB-p65) protein was also tested. TNF-α-treated NPCs cultured with the RADA16-I peptide showed up-regulated gene expression for matrix-degrading enzymes, such as matrix metalloproteinases-3 (MMP-3), MMP-9, and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-4), and down-regulated gene expression for ECM proteins such as aggrecan, collagen II, and Sox-9. The RADA-KPSS peptide could attenuate the expression of MMP-3, MMP-9, and ADAMTS-4, promote accumulation of ECM proteins, and increase secretion of glycosaminoglycan as compared with the RADA16-I peptide. Moreover, the TNF-α-damaged NPCs was further demonstrated to inhibit NF-κB-p65, IL-1, IL-6, and prostaglandin E-2 proteins and decrease cell apoptosis in RADA-KPSS peptide. In conclusion, the functional self-assembled RADA-KPSS peptides have anti-inflammatory and anti-apoptotic effects by promoting anabolic processes and inhibiting catabolic processes in intervertebral disk degeneration. These peptides may be feasible for clinical applications in NP tissue engineering. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1082-1091, 2018.

TNF‐α enhances apoptosis by promoting chop expression in nucleus pulposus cells: role of the MAPK and NF‐κB pathways

“…A previous study by Li et al showed that TNF‐α induces apoptosis in NP cells. Zhang demonstrated that lentiviral shRNA silencing of CHOP partly suppressed disc cell apoptosis.…”

Overexpression of miR-140-5p inhibits lipopolysaccharide-induced human intervertebral disc inflammation and degeneration by downregulating toll-like receptor 4

“…TNF-α can enhance matrix-degrading enzyme activity and increase NP cell apoptosis (17,22,23). Li et al also reported that TNF-α induced NP cell inflammation and apoptosis by activating NF-κB signalling (24). Heme oxygenase-1 (HO-1) has also been reported to participate in the cellular anti-inflammatory processes relating to IVD degeneration (25).…”

Differentiated adipose‐derived stem cell cocultures for bone regeneration in RADA16‐I in vitro

“…to promote cell migration, proliferation, and differentiation (Li et al, 2017;Liu et al, 2013). In addition, these functionalized self-assembling peptide nanofibre scaffolds have been reported to exhibit extensive potential for bone, vascular, and neural regeneration (Bradshaw et al, 2014;Maleki, Natalello, Pugliese, & Gelain, 2017;Wang et al, 2015).…”