Inhibition of interleukin‑1β‑stimulated matrix metalloproteinases via the controlled release of interleukin‑1Ra from chitosan microspheres in chondrocytes

Zhou,Pang‑Hu; Ma,Bei‑Lei; Shi,Lei; Xie,Ting; Qiu,Bo

doi:10.3892/mmr.2014.2743

Inhibition of interleukin‑1β‑stimulated matrix metalloproteinases via the controlled release of interleukin‑1Ra from chitosan microspheres in chondrocytes

Authors:
- Pang‑Hu Zhou
- Bei‑Lei Ma
- Lei Shi
- Ting Xie
- Bo Qiu
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Affiliations: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China, Department of Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China, Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China, Department of Women Health Care, Hubei Women and Children's Hospital, Wuhan, Hubei 430070, P.R. China
Published online on: October 22, 2014 https://doi.org/10.3892/mmr.2014.2743
Pages: 555-560

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Abstract

The aim of the study was to determine whether the controlled release of interleukin (IL)‑1Ra from chitosan (CS) microspheres inhibits the IL‑1β‑stimulated production of matrix metalloproteinases (MMPs) in chondrocytes. The CS‑IL‑1Ra microspheres were fabricated by an emulsification method using sodium tripolyphosphate as a crosslinker, and the controlled release of IL‑1Ra was determined using an enzyme‑linked immunosorbent assay. IL‑1β was added to normal rat chondrocytes to stimulate MMP production. The chondrocytes were incubated with CS‑IL‑1Ra microspheres to assess its effects on IL‑1β‑induced MMP expression. Chondrocyte proliferation and glycosaminoglycan (GAG) content were also determined. The mRNA expression and protein levels of IL‑1β, MMP‑1, MMP‑3 and MMP‑13 were detected using reverse transcription‑polymerase chain reaction and western blotting analyses, respectively. The IL‑1Ra release kinetics were characterized by an initial burst release, which was reduced to a linear release over seven days. The mRNA expression levels and protein levels of IL‑1β, MMP‑1, MMP‑3 and MMP‑13 were reduced compared with the control group. The present study demonstrated the chondroprotective properties of CS microspheres as a controlled release system carrying IL‑1Ra, due to the ability of the system to downregulate the expression of osteoarthritis‑associated matrix‑degrading proteinases in chondrocytes.

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