PMID- 30603552 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200225 IS - 2212-5469 (Electronic) IS - 1738-2696 (Print) IS - 1738-2696 (Linking) VI - 15 IP - 3 DP - 2018 Jun TI - In Vitro Anti-Inflammation and Chondrogenic Differentiation Effects of Inclusion Nanocomplexes of Hyaluronic Acid-Beta Cyclodextrin and Simvastatin. PG - 263-274 LID - 10.1007/s13770-018-0119-9 [doi] AB - The aim of this study was to prepare inclusion nanocomplexes of hyaluronic acid-beta-cyclodextrin and simvastatin (HA-beta-CD/SIM) and evaluate in vitro anti-inflammation effects on lipopolysaccharide (LPS)-activated synoviocytes and chondrogenic differentiation effects on rat adipose-derived stem cells (rADSCs). The beta-CD moieties in HA-beta-CD could incorporate SIM to form HA-beta-CD/SIM nanocomplexes with diameters of 297-350 nm. HA-beta-CD/SIM resulted in long-term release of SIM from the nanocomplexes for up to 63 days in a sustained manner. In vitro studies revealed that HA-beta-CD/SIM nanocomplexes were able to effectively and dose-dependently suppress the mRNA expression levels of pro-inflammatory markers such as matrix metallopeptidase-3 (MMP-3), MMP-13, cyclooxygenase-2 (COX-2), a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), interleukin-6 (IL-6), and tumor necrosis factor (TNF-alpha) in LPS-stimulated synoviocytes. HA-beta-CD/SIM-treated rADSCs significantly and dose-dependently enhanced mRNA expressions of aggrecan, collagen type II (COL2A1), and collagen type X (COL10A1), implying that HA-beta-CD/SIM greatly induced the chondrogenic differentiation of rADSCs. Conclusively, HA-beta-CD/SIM nanocomplexes will be a promising therapeutic material to alleviate inflammation as well as promote chondrogenesis. FAU - Kim, Tae-Hoon AU - Kim TH AD - 1Department of Orthopedic Surgery, Konkuk University School of Medicine, 120-1 Neungdong-ro, Hwayang-dong, Gwangjin-gu, Seoul, 05029 Korea. ISNI: 0000 0004 0532 8339. GRID: grid.258676.8 FAU - Yun, Young-Pil AU - Yun YP AD - 2Department of Orthopedic Surgery and Rare Diseases Institute, Korea University Guro Hospital, Korea University College of Medicine, #148, Guro-dong, Guro-gu, Seoul, 08308 Korea. ISNI: 0000 0001 0840 2678. GRID: grid.222754.4 FAU - Shim, Kyu-Sik AU - Shim KS AD - 2Department of Orthopedic Surgery and Rare Diseases Institute, Korea University Guro Hospital, Korea University College of Medicine, #148, Guro-dong, Guro-gu, Seoul, 08308 Korea. ISNI: 0000 0001 0840 2678. GRID: grid.222754.4 AD - 3Department of Biomedical Science, Korea University College of Medicine, Korea University, Anam-dong, Seongbuk-gu, Seoul, 02841 Korea. ISNI: 0000 0001 0840 2678. GRID: grid.222754.4 FAU - Kim, Hak-Jun AU - Kim HJ AD - 2Department of Orthopedic Surgery and Rare Diseases Institute, Korea University Guro Hospital, Korea University College of Medicine, #148, Guro-dong, Guro-gu, Seoul, 08308 Korea. ISNI: 0000 0001 0840 2678. GRID: grid.222754.4 FAU - Kim, Sung Eun AU - Kim SE AD - 2Department of Orthopedic Surgery and Rare Diseases Institute, Korea University Guro Hospital, Korea University College of Medicine, #148, Guro-dong, Guro-gu, Seoul, 08308 Korea. ISNI: 0000 0001 0840 2678. GRID: grid.222754.4 FAU - Park, Kyeongsoon AU - Park K AD - 4Department of Systems Biotechnology, College of Biotechnology and Natural Resources, Chung-Ang University, 4726 Seodong-daero, Daedeok-myeon, Anseong-si, Gyeonggi-do 17546 Korea. ISNI: 0000 0001 0789 9563. GRID: grid.254224.7 FAU - Song, Hae-Ryong AU - Song HR AD - 2Department of Orthopedic Surgery and Rare Diseases Institute, Korea University Guro Hospital, Korea University College of Medicine, #148, Guro-dong, Guro-gu, Seoul, 08308 Korea. ISNI: 0000 0001 0840 2678. GRID: grid.222754.4 LA - eng PT - Journal Article DEP - 20180503 PL - Korea (South) TA - Tissue Eng Regen Med JT - Tissue engineering and regenerative medicine JID - 101699923 PMC - PMC6171684 OTO - NOTNLM OT - Adipose-derived stem cells OT - Chondrogenesis OT - Hyaluronic acid-beta-cyclodextrin OT - Simvastatin COIS- The authors declare no conflict of interest.Animal experimental procedures were approved by the Institutional Animal Care and Use Committee of the Korea University Medical Center (KUIACUC-2014-268 and KUIACUC-2014-5). EDAT- 2019/01/04 06:00 MHDA- 2019/01/04 06:01 PMCR- 2019/05/03 CRDT- 2019/01/04 06:00 PHST- 2017/12/11 00:00 [received] PHST- 2018/02/26 00:00 [revised] PHST- 2018/04/06 00:00 [accepted] PHST- 2019/01/04 06:00 [entrez] PHST- 2019/01/04 06:00 [pubmed] PHST- 2019/01/04 06:01 [medline] PHST- 2019/05/03 00:00 [pmc-release] AID - 119 [pii] AID - 10.1007/s13770-018-0119-9 [doi] PST - epublish SO - Tissue Eng Regen Med. 2018 May 3;15(3):263-274. doi: 10.1007/s13770-018-0119-9. eCollection 2018 Jun.