PMID- 28851291 OWN - NLM STAT- MEDLINE DCOM- 20180511 LR - 20220408 IS - 1471-2121 (Electronic) IS - 1471-2121 (Linking) VI - 18 IP - 1 DP - 2017 Aug 29 TI - Honokiol improved chondrogenesis and suppressed inflammation in human umbilical cord derived mesenchymal stem cells via blocking nuclear factor-kappaB pathway. PG - 29 LID - 10.1186/s12860-017-0145-9 [doi] LID - 29 AB - BACKGROUND: Cartilage degradation is the significant pathological process in osteoarthritis (OA). Inflammatory cytokines, such as interleukin-1beta (IL-1beta), activate various downstream mediators contributing to OA pathology. Recently, stem cell-based cartilage repair emerges as a potential therapeutic strategy that being widely studied, whereas, the outcome is still far from clinical application. In this study, we focused on an anti-inflammatory agent, honokiol, which is isolated from an herb, investigated the potential effects on human umbilical cord derived mesenchymal stem cells (hUC-MSCs) in IL-1beta stimulation. METHODS: Second passage hUC-MSCs were cultured for multi-differentiation. Flow cytometry, qRT-PCR, von Kossa stain, alcian blue stain and oil red O stain were used for characterization and multi-differentiation determination. Honokiol (5, 10, 25, 50 muM) and IL-1beta (10 ng/ml) were applied in hUC-MSCs during chondrogenesis. Analysis was performed by MTT, cell apoptosis evaluation, ELISA assay, qRT-PCR and western blot. RESULTS: hUC-MSC was positive for CD73, CD90 and CD105, but lack of CD34 and CD45. Remarkable osteogenesis, chondrogenesis and adipogenesis were detected in hUC-MSCs. IL-1beta enhanced cell apoptosis and necrosis and activated the expression of caspase-3, cyclooxygenase-2 (COX-2), interleukin-6 (IL-6) and matrix metalloproteinase (MMP)-1, -9, 13 in hUC-MSCs. Moreover, the expression of SRY-related high-mobility group box 9 (SOX-9), aggrecan and col2alpha1 was suppressed. Honokiol relieved these negative impacts induced by IL-1beta and suppressed Nuclear factor-kappaB (NF-kappaB) pathway by downregulating expression of p-IKKalpha/beta, p-IkappaBalpha and p-p65 in dose-dependent and time-dependent manner. CONCLUSIONS: Honokiol improved cell survival and chondrogenesis of hUC-MSCs and inhibited IL-1beta-induced inflammatory response, which suggested that combination of anti-inflammation and stem cell can be a novel strategy for better cartilage repair. FAU - Wu, Hao AU - Wu H AD - Department of Orthopaedics, The First Affiliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, 710061, People's Republic of China. FAU - Yin, Zhanhai AU - Yin Z AD - Department of Orthopaedics, The First Affiliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, 710061, People's Republic of China. FAU - Wang, Ling AU - Wang L AD - Center for Biomedical Engineering and Regenerative Medicine, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, People's Republic of China. FAU - Li, Feng AU - Li F AD - Department of Orthopaedics, The First Affiliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, 710061, People's Republic of China. FAU - Qiu, Yusheng AU - Qiu Y AD - Department of Orthopaedics, The First Affiliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, 710061, People's Republic of China. yusheng.qiu@mail.xjtu.edu.cn. LA - eng PT - Journal Article DEP - 20170829 PL - England TA - BMC Cell Biol JT - BMC cell biology JID - 100966972 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Biphenyl Compounds) RN - 0 (IL6 protein, human) RN - 0 (Interleukin-6) RN - 0 (Lignans) RN - 0 (NF-kappa B) RN - 11513CCO0N (honokiol) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 1.14.99.1 (PTGS2 protein, human) RN - EC 3.4.22.- (CASP3 protein, human) RN - EC 3.4.22.- (Caspase 3) RN - EC 3.4.24.- (Collagenases) SB - IM MH - Anti-Inflammatory Agents/*pharmacology MH - Apoptosis/drug effects MH - Biphenyl Compounds/*pharmacology MH - Caspase 3/genetics/metabolism MH - Cell Differentiation/drug effects MH - Cell Survival/drug effects MH - Cells, Cultured MH - Chondrogenesis/*drug effects MH - Collagenases/genetics/metabolism MH - Cyclooxygenase 2/genetics/metabolism MH - Gene Expression Regulation/drug effects MH - Humans MH - Inflammation/genetics/*metabolism MH - Interleukin-6/metabolism MH - Lignans/*pharmacology MH - Mesenchymal Stem Cells/cytology MH - NF-kappa B/*metabolism MH - Signal Transduction/drug effects PMC - PMC5576244 OTO - NOTNLM OT - Cartilage repair OT - Honokiol OT - Interleukin-1beta OT - Mesenchymal stem cell OT - Osteoarthritis COIS- CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declared that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2017/08/31 06:00 MHDA- 2018/05/12 06:00 PMCR- 2017/08/29 CRDT- 2017/08/31 06:00 PHST- 2017/02/19 00:00 [received] PHST- 2017/08/20 00:00 [accepted] PHST- 2017/08/31 06:00 [entrez] PHST- 2017/08/31 06:00 [pubmed] PHST- 2018/05/12 06:00 [medline] PHST- 2017/08/29 00:00 [pmc-release] AID - 10.1186/s12860-017-0145-9 [pii] AID - 145 [pii] AID - 10.1186/s12860-017-0145-9 [doi] PST - epublish SO - BMC Cell Biol. 2017 Aug 29;18(1):29. doi: 10.1186/s12860-017-0145-9.