In Vitro Anti-Inflammation and Chondrogenic Differentiation Effects of Inclusion Nanocomplexes of Hyaluronic Acid-Beta Cyclodextrin and Simvastatin.
10.1007/s13770-018-0119-9
- Author:
Tae Hoon KIM
1
;
Young Pil YUN
;
Kyu Sik SHIM
;
Hak Jun KIM
;
Sung Eun KIM
;
Kyeongsoon PARK
;
Hae Ryong SONG
Author Information
1. Department of Orthopedic Surgery, Konkuk University School of Medicine, 120-1 Neungdong-ro, Hwayang-dong, Gwangjin-gu, Seoul 05029, Korea.
- Publication Type:Original Article
- Keywords:
Hyaluronic acid-β-cyclodextrin;
Simvastatin;
Chondrogenesis;
Adipose-derived stem cells
- MeSH:
Aggrecans;
Animals;
Chondrogenesis;
Collagen Type II;
Collagen Type X;
Cyclooxygenase 2;
In Vitro Techniques*;
Inflammation;
Interleukin-6;
Rats;
RNA, Messenger;
Simvastatin*;
Stem Cells;
Thrombospondins;
Tumor Necrosis Factor-alpha
- From:
Tissue Engineering and Regenerative Medicine
2018;15(3):263-274
- CountryRepublic of Korea
- Language:English
-
Abstract:
The aim of this study was to prepare inclusion nanocomplexes of hyaluronic acid-β-cyclodextrin and simvastatin (HA-β-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 β-CD moieties in HA-β-CD could incorporate SIM to form HA-β-CD/SIM nanocomplexes with diameters of 297–350 nm. HA-β-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-β-CD/SIM nanocomplexes were able to effectively and dose-dependently suppress the mRNA expression levels of proinflammatory 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-α) in LPS-stimulated synoviocytes. HA-β-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-β-CD/SIM greatly induced the chondrogenic differentiation of rADSCs. Conclusively, HA-β-CD/SIM nanocomplexes will be a promising therapeutic material to alleviate inflammation as well as promote chondrogenesis.