This paper presents a new method of delivering shRNA with biodegradable, thermosensitive PLGA-PEG-PLGA hydrogels for gene treatment of osteoarthritis （OA）. OA is a chronic debilitating disease. Without the proper tr...This paper presents a new method of delivering shRNA with biodegradable, thermosensitive PLGA-PEG-PLGA hydrogels for gene treatment of osteoarthritis （OA）. OA is a chronic debilitating disease. Without the proper treatment and prognosis, it may result in the loss of joint function in aged people. Currently, gene therapy targeted on WISP-1 has emerged as an alternative method for OA treatment. In order to constantly release shRNA at 37.0 ℃, we synthetized the hydrogels via ring-opening copolymerization of lactide （LA） and glycolide （GA） using Polyethylene glycol （PEG Mn = 1000） and stannous octoate （Sn（Oct）2, 95%） as the macroinitiator and catalyst. First, the PLGA-PEG-PLGA copolymer was mixed with WISP- 1 shRNA and PEI-Lys in distilled water at 4.0 ℃. Then, the WISP-lshRNA/PEI-Lys loaded hydrogel was formed after incubation of the mixed solution at 37.0 ℃. During tests, the plasmid was released from this hydrogel complex constantly, and enhanced the transfection efficiency of WISP-1 shRNA. In addition, silencing WISP-1 results to lower expression of MMP-3 and ADAMTS, and the accumulation of HBP 1 in synoviocytes. Therefore, the hydrogel containing WISP-1 shRNA is demonstrated an efficient way for the treatment of OA.展开更多
基金Project supported by the National Natural Science Foundation of China （Grant No. 51273081） and Changchun Science and Technology Plan Project （Grant No. 12SF20） and Graduate Innovation Fund of Jilin University project （ No. 20121112）.
文摘This paper presents a new method of delivering shRNA with biodegradable, thermosensitive PLGA-PEG-PLGA hydrogels for gene treatment of osteoarthritis （OA）. OA is a chronic debilitating disease. Without the proper treatment and prognosis, it may result in the loss of joint function in aged people. Currently, gene therapy targeted on WISP-1 has emerged as an alternative method for OA treatment. In order to constantly release shRNA at 37.0 ℃, we synthetized the hydrogels via ring-opening copolymerization of lactide （LA） and glycolide （GA） using Polyethylene glycol （PEG Mn = 1000） and stannous octoate （Sn（Oct）2, 95%） as the macroinitiator and catalyst. First, the PLGA-PEG-PLGA copolymer was mixed with WISP- 1 shRNA and PEI-Lys in distilled water at 4.0 ℃. Then, the WISP-lshRNA/PEI-Lys loaded hydrogel was formed after incubation of the mixed solution at 37.0 ℃. During tests, the plasmid was released from this hydrogel complex constantly, and enhanced the transfection efficiency of WISP-1 shRNA. In addition, silencing WISP-1 results to lower expression of MMP-3 and ADAMTS, and the accumulation of HBP 1 in synoviocytes. Therefore, the hydrogel containing WISP-1 shRNA is demonstrated an efficient way for the treatment of OA.
