PMID- 34993189 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220108 IS - 2296-4185 (Print) IS - 2296-4185 (Electronic) IS - 2296-4185 (Linking) VI - 9 DP - 2021 TI - Establishment of an Ex Vivo Inflammatory Osteoarthritis Model With Human Osteochondral Explants. PG - 787020 LID - 10.3389/fbioe.2021.787020 [doi] LID - 787020 AB - Osteoarthritis (OA) is the most common degenerative joint disease without clear pathophysiological mechanism and effective drugs for treatment. Although various animal models exist, the translation of the outcome into clinics remains difficult due to species differences. In this study, an ex vivo inflammatory OA model was induced using different concentrations of interleukin one beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) on explants from the human femoral head. In the inflammatory OA groups, the gene expression levels of cartilage catabolism (matrix metalloproteinase 1 (MMP1), matrix metalloproteinase 3 (MMP3)), and inflammation (interleukin 6 (IL-6), interleukin 8 (IL-8)) markers were significantly upregulated, while the anabolic genes (collagen 2 (COL2), aggrecan (ACAN), and proteoglycan 4 (PRG4)) were downregulated compared to the control group. The release of cytokines (IL-6, IL-8) and nitric oxide (NO) in the conditioned medium was also upregulated in inflammatory OA groups. The Safranin O/Fast Green staining showed loss of proteoglycan in the superficial zone cartilage after cytokine treatment. The results indicated that an ex vivo inflammation and degeneration model was successfully established using osteochondral explants from the human femoral head. This model can be used to elucidate the in-depth mechanism of inflammatory OA and to screen new drugs for OA treatment. CI - Copyright (c) 2021 Li, Zhang, Zhu, Alini, Grad and Li. FAU - Li, Kaihu AU - Li K AD - Department of Orthopaedics, Xiangya Hospital of Central South University, Changsha, China. AD - AO Research Institute Davos, Davos, Switzerland. FAU - Zhang, Penghui AU - Zhang P AD - AO Research Institute Davos, Davos, Switzerland. AD - Department of Orthopaedic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China. FAU - Zhu, Yong AU - Zhu Y AD - Department of Orthopaedics, Xiangya Hospital of Central South University, Changsha, China. FAU - Alini, Mauro AU - Alini M AD - AO Research Institute Davos, Davos, Switzerland. FAU - Grad, Sibylle AU - Grad S AD - AO Research Institute Davos, Davos, Switzerland. FAU - Li, Zhen AU - Li Z AD - AO Research Institute Davos, Davos, Switzerland. LA - eng PT - Journal Article DEP - 20211221 PL - Switzerland TA - Front Bioeng Biotechnol JT - Frontiers in bioengineering and biotechnology JID - 101632513 PMC - PMC8724558 OTO - NOTNLM OT - ex vivo OT - human OT - inflammation OT - model OT - osteoarthritis OT - osteochondral explant COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/01/08 06:00 MHDA- 2022/01/08 06:01 PMCR- 2021/01/01 CRDT- 2022/01/07 06:28 PHST- 2021/09/30 00:00 [received] PHST- 2021/11/25 00:00 [accepted] PHST- 2022/01/07 06:28 [entrez] PHST- 2022/01/08 06:00 [pubmed] PHST- 2022/01/08 06:01 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 787020 [pii] AID - 10.3389/fbioe.2021.787020 [doi] PST - epublish SO - Front Bioeng Biotechnol. 2021 Dec 21;9:787020. doi: 10.3389/fbioe.2021.787020. eCollection 2021.