PMID- 31694744 OWN - NLM STAT- MEDLINE DCOM- 20200917 LR - 20200917 IS - 0392-856X (Print) IS - 0392-856X (Linking) VI - 38 IP - 4 DP - 2020 Jul-Aug TI - Soluble IL-6R promotes chondrogenic differentiation of mesenchymal stem cells to enhance the repair of articular cartilage defects using a rat model for rheumatoid arthritis. PG - 670-679 AB - OBJECTIVES: Although articular cartilage contributes to smooth joint motion, once damaged this functionality cannot be recovered. Activation of the IL-6/STAT3 signalling pathway contributes to chondrogenic differentiation of mesenchymal stem cells (MSCs), indicating a role for soluble IL-6R (sIL-6R) during chondrogenesis in vitro. The aim of this study is to develop a novel therapeutic tool for regenerative medicine of articular cartilage. METHODS: Human bone marrow-derived MSCs were pre-treated with sIL-6R to direct their differentiation into chondrocytes, then seeded on a poly-lactic-co-glycolic acid (PLGA) sheet to enhance the localised residence of MSCs. The material was implanted into knee joint spaces of antigen-induced arthritis (AIA) rats, an animal model of rheumatoid arthritis (RA). After 8 weeks, the effects of the implantation on articular cartilage repair were assessed by x-ray image and staining with safranin O (S-O), aggrecan and human leukocyte antigen (HLA). RESULTS: Swelling of knees in AIA rats, but not sham-treated rats, was observed. AIA rats implanted with PLGA and sIL-6R-treated MSCs showed similar knee joint imaging to sham rats using x-ray; however, those with PLGA alone, or with PLGA with MSCs, did not. Rats implanted with PLGA and sIL-6R-treated MSCs, but not PLGA alone or PLGA with MSCs, showed positive imaging by S-O staining as well as human aggrecan. HLA was not detected in the knees of any of the rats. CONCLUSIONS: PLGA and sIL-6R-treated MSCs help to repair articular cartilage with high efficacy. Thus, the application of this promising strategy to regenerative medicine for articular cartilage in patients with RA is anticipated. FAU - Yamagata, Kaoru AU - Yamagata K AD - The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. FAU - Nakayamada, Shingo AU - Nakayamada S AD - The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. FAU - Zhang, Tong AU - Zhang T AD - The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. FAU - Zhang, Xiangmei AU - Zhang X AD - Research Center, The Fourth Hospital of Hebei Medical University and The Tumor Hospital of Hebei Province, Shijiazhuang, China. FAU - Tanaka, Yoshiya AU - Tanaka Y AD - The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. tanaka@med.uoeh-u.ac.jp. LA - eng PT - Journal Article DEP - 20191030 PL - Italy TA - Clin Exp Rheumatol JT - Clinical and experimental rheumatology JID - 8308521 SB - IM MH - Animals MH - *Arthritis, Rheumatoid MH - *Cartilage, Articular MH - Cell Differentiation MH - Cells, Cultured MH - Chondrogenesis MH - Humans MH - *Mesenchymal Stem Cell Transplantation MH - *Mesenchymal Stem Cells MH - Rats EDAT- 2019/11/07 06:00 MHDA- 2020/09/18 06:00 CRDT- 2019/11/08 06:00 PHST- 2019/05/22 00:00 [received] PHST- 2019/09/04 00:00 [accepted] PHST- 2019/11/07 06:00 [pubmed] PHST- 2020/09/18 06:00 [medline] PHST- 2019/11/08 06:00 [entrez] AID - 14340 [pii] PST - ppublish SO - Clin Exp Rheumatol. 2020 Jul-Aug;38(4):670-679. Epub 2019 Oct 30.