Tissue Eng Regen Med.  2018 Jun;15(3):263-274. 10.1007/s13770-018-0119-9.

In Vitro Anti-Inflammation and Chondrogenic Differentiation Effects of Inclusion Nanocomplexes of Hyaluronic Acid-Beta Cyclodextrin and Simvastatin

Affiliations
  • 1Department of Orthopedic Surgery, Konkuk University School of Medicine, 120-1 Neungdong-ro, Hwayang-dong, Gwangjin-gu, Seoul 05029, Korea.
  • 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. sekim10@korea.ac.kr, songhae@korea.ac.kr
  • 3Department of Biomedical Science, Korea University College of Medicine, Korea University, Anam-dong, Seongbuk-gu, Seoul 02841, Korea.
  • 4Department of Systems Biotechnology, College of Biotechnology and Natural Resources, Chung-Ang University, 4726 Seodong-daero, Daedeok-myeon, Anseong-si, Gyeonggi-do 17546, Korea. kspark1223@cau.ac.kr

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.

Keyword

Hyaluronic acid-β-cyclodextrin; Simvastatin; Chondrogenesis; Adipose-derived stem cells

MeSH Terms

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
Aggrecans
Collagen Type II
Collagen Type X
Cyclooxygenase 2
Interleukin-6
RNA, Messenger
Simvastatin
Thrombospondins
Tumor Necrosis Factor-alpha
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