title: Inhibition of interleukin-1β-stimulated matrix metalloproteinases via the controlled release of interleukin-1Ra from chitosan microspheres in chondrocytes.
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.
authors.affiliation: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Pang-Hu
authors.initials: PH
authors.lastname: Zhou
authors.affiliation: Department of Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Bei-Lei
authors.initials: BL
authors.lastname: Ma
authors.affiliation: Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Women Health Care, Hubei Women and Children's Hospital, Wuhan, Hubei 430070, P.R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Xie
authors.affiliation: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Qiu
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism*; D003692:Delayed-Action Preparations; D053590:Interleukin 1 Receptor Antagonist Protein / Q000737:chemistry / Q000493:pharmacokinetics*; D053583:Interleukin-1beta / Q000378:metabolism* / Q000494:pharmacology; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008863:Microspheres; D051381:Rats
chemical_list: D003692:Delayed-Action Preparations; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D048271:Chitosan; D020782:Matrix Metalloproteinases