PMID- 38247922 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240128 IS - 2306-5354 (Print) IS - 2306-5354 (Electronic) IS - 2306-5354 (Linking) VI - 11 IP - 1 DP - 2024 Jan 1 TI - Nuclear Factor-kappaB Decoy Oligodeoxynucleotide Attenuates Cartilage Resorption In Vitro. LID - 10.3390/bioengineering11010046 [doi] LID - 46 AB - BACKGROUND: Cartilage harvest and transplantation is a common surgery using costal, auricular, and septal cartilage for craniofacial reconstruction. However, absorption and warping of the cartilage grafts can occur due to inflammatory factors associated with wound healing. Transcription factor nuclear factor-kappaB (NF-kappaB) is activated by the various stimulation such as interleukin-1 (IL-1), and plays a central role in the transactivation of this inflammatory cytokine gene. Inhibition of NF-kappaB may have anti-inflammatory effects. The aim of this study was to explore the potential of an NF-kappaB decoy oligodeoxynucleotide (Decoy) as a chondroprotective agent. MATERIALS AND METHODS: Safe and efficacious concentrations of Decoy were assessed using rabbit nasal septal chondrocytes (rNSChs) and assays for cytotoxicity, proteoglycan (PG) synthesis, and PG turnover were carried out. The efficacious concentration of Decoy determined from the rNSChs was then applied to human nasal septal cartilage (hNSC) in vitro and analyzed for PG turnover, the levels of inflammatory markers, and catabolic enzymes in explant-conditioned culture medium. RESULTS: Over the range of Decoy conditions and concentrations, no inhibition of PG synthesis or cytotoxicity was observed. Decoy at 10 muM effectively inhibited PG degradation in the hNSC explant, prolonging PG half-life by 63% and decreasing matrix metalloprotease 3 (MMP-3) by 70.7% (p = 0.027). CONCLUSIONS: Decoy may be considered a novel chondroprotective therapeutic agent in cartilage transplantation due to its ability to inhibit cartilage degradation due to inflammation cytokines. FAU - Nemoto, Hitoshi AU - Nemoto H AD - Department of Otolaryngology-Head and Neck Surgery, School of Medicine, University of California, La Jolla, San Diego, CA 92093, USA. AD - Department of Plastic Surgery, School of Medicine, Tokai University, Isehara 259-1193, Kanagawa, Japan. FAU - Sakai, Daisuke AU - Sakai D AUID- ORCID: 0000-0003-4189-9270 AD - Department of Orthopaedic Surgery, School of Medicine, University of California, La Jolla, San Diego, CA 92093, USA. AD - Department of Orthopaedic Surgery, School of Medicine, Tokai University, Isehara 259-1193, Kanagawa, Japan. FAU - Watson, Deborah AU - Watson D AD - Department of Otolaryngology-Head and Neck Surgery, School of Medicine, University of California, La Jolla, San Diego, CA 92093, USA. FAU - Masuda, Koichi AU - Masuda K AUID- ORCID: 0000-0002-5361-4415 AD - Department of Orthopaedic Surgery, School of Medicine, University of California, La Jolla, San Diego, CA 92093, USA. LA - eng PT - Journal Article DEP - 20240101 PL - Switzerland TA - Bioengineering (Basel) JT - Bioengineering (Basel, Switzerland) JID - 101676056 PMC - PMC10813736 OTO - NOTNLM OT - cartilage OT - decoy oligodeoxynucleotide OT - nuclear factor-kappab OT - resorption COIS- K.M. has received research non-related grants from AnGes inc. K.M. and D.S. have been involved as consultants in AnGes Inc. for different applications. H.N. and D.W. have no conflicts of interest. EDAT- 2024/01/22 06:43 MHDA- 2024/01/22 06:44 PMCR- 2024/01/01 CRDT- 2024/01/22 04:34 PHST- 2023/10/25 00:00 [received] PHST- 2023/12/20 00:00 [revised] PHST- 2023/12/22 00:00 [accepted] PHST- 2024/01/22 06:44 [medline] PHST- 2024/01/22 06:43 [pubmed] PHST- 2024/01/22 04:34 [entrez] PHST- 2024/01/01 00:00 [pmc-release] AID - bioengineering11010046 [pii] AID - bioengineering-11-00046 [pii] AID - 10.3390/bioengineering11010046 [doi] PST - epublish SO - Bioengineering (Basel). 2024 Jan 1;11(1):46. doi: 10.3390/bioengineering11010046.