PMID- 29164771 OWN - NLM STAT- MEDLINE DCOM- 20190815 LR - 20220317 IS - 1552-4965 (Electronic) IS - 1549-3296 (Linking) VI - 106 IP - 4 DP - 2018 Apr TI - Functional self-assembled peptide scaffold inhibits tumor necrosis factor-alpha-induced inflammation and apoptosis in nucleus pulposus cells by suppressing nuclear factor-kappaB signaling. PG - 1082-1091 LID - 10.1002/jbm.a.36301 [doi] AB - 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-alpha) has not been studied. Therefore, we cultured NPCs treated with TNF-alpha 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-kappaB-p65 (NF-kappaB-p65) protein was also tested. TNF-alpha-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-alpha-damaged NPCs was further demonstrated to inhibit NF-kappaB-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. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1082-1091, 2018. CI - (c) 2017 Wiley Periodicals, Inc. FAU - Li, Xiaochuan AU - Li X AD - Department of Orthopedic Surgery, Navy General Hospital, Beijing, People's Republic of China. AD - Department of Orthopedic Surgery, The People's Hospital of Gaozhou, Guangdong, People's Republic of China. FAU - Cheng, Shi AU - Cheng S AD - Department of Orthopedic Surgery, Navy General Hospital, Beijing, People's Republic of China. FAU - Wu, Yaohong AU - Wu Y AD - Department of Orthopedic Surgery, Navy General Hospital, Beijing, People's Republic of China. AD - Department of Spinal Surgery, The Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, Jiangxi, People's Republic of China. FAU - Ying, Jingwei AU - Ying J AD - Department of Orthopedic Surgery, Navy General Hospital, Beijing, People's Republic of China. FAU - Wang, Chaofeng AU - Wang C AD - Department of Orthopedic Surgery, Navy General Hospital, Beijing, People's Republic of China. FAU - Wen, Tianyong AU - Wen T AD - Department of Orthopedic Surgery, Navy General Hospital, Beijing, People's Republic of China. FAU - Bai, Xuedong AU - Bai X AD - Department of Orthopedic Surgery, Navy General Hospital, Beijing, People's Republic of China. FAU - Ji, Wei AU - Ji W AD - Department of Orthopedic Surgery, Navy General Hospital, Beijing, People's Republic of China. FAU - Wang, Deli AU - Wang D AD - Department of Orthopedic Surgery, Navy General Hospital, Beijing, People's Republic of China. FAU - Ruan, Dike AU - Ruan D AD - Department of Orthopedic Surgery, Navy General Hospital, Beijing, People's Republic of China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20171228 PL - United States TA - J Biomed Mater Res A JT - Journal of biomedical materials research. Part A JID - 101234237 RN - 0 (Glycosaminoglycans) RN - 0 (Inflammation Mediators) RN - 0 (NF-kappa B) RN - 0 (Peptides) RN - 0 (Tumor Necrosis Factor-alpha) RN - 139874-52-5 (NF-KappaB Inhibitor alpha) MH - Adult MH - *Apoptosis/drug effects MH - Extracellular Matrix/metabolism MH - Gene Expression Regulation/drug effects MH - Glycosaminoglycans/metabolism MH - Humans MH - Inflammation/*pathology MH - Inflammation Mediators/metabolism MH - Male MH - Middle Aged MH - NF-KappaB Inhibitor alpha/metabolism MH - NF-kappa B/*metabolism MH - Nanofibers/chemistry MH - Nucleus Pulposus/drug effects/*pathology MH - Peptides/*pharmacology MH - *Signal Transduction MH - Tissue Scaffolds/*chemistry MH - Tumor Necrosis Factor-alpha/*adverse effects OTO - NOTNLM OT - anti-inflammation OT - intervertebral disk OT - self-assembly peptide OT - tissue engineering EDAT- 2017/11/23 06:00 MHDA- 2019/08/16 06:00 CRDT- 2017/11/23 06:00 PHST- 2017/09/06 00:00 [received] PHST- 2017/10/28 00:00 [revised] PHST- 2017/11/14 00:00 [accepted] PHST- 2017/11/23 06:00 [pubmed] PHST- 2019/08/16 06:00 [medline] PHST- 2017/11/23 06:00 [entrez] AID - 10.1002/jbm.a.36301 [doi] PST - ppublish SO - J Biomed Mater Res A. 2018 Apr;106(4):1082-1091. doi: 10.1002/jbm.a.36301. Epub 2017 Dec 28.