title: Intra-articular lentivirus-mediated insertion of the fat-1 gene ameliorates osteoarthritis.
abstract: Osteoarthritis (OA) is a gradually progressive degenerative disease characterized by gradual inflammatory loss of articular cartilage caused by increased proteolytic catabolism, mediated by interleukin-1 (IL-1), tumor necrosis factor α (TNF-α), matrix metalloproteinase (MMPs), aggrecanases and other proteinases, and reduced anabolism of cartilage components, contributed by interleukin-4 (IL-4), interleukin-10 (IL-10), insulin-like growth factor 1 (IGF-1), transforming growth factor β (TGF-β), and bone morphogenetic proteins (BMPs). Substantial studies showed n-3 polyunsaturated fatty acids (n-3 PUFAs) exhibit a powerful anti-inflammatory effects in and ex vivo through reducing the production of IL-1 and TNF-α and increasing the expression of IL-4, IL-10, TGF-β and IGF-1 in OA. Meanwhile, more convincing results are observed in the fat-1 transgenic mice, which are exogenously inserted in a fat-1 gene from Caenorhabditis elegans, which can endogenously convert n-6 polyunsaturated fatty acids (n-6 PUFAs) to n-3 PUFAs. Taken together, it has long been realized that dietary supplementation with fish oils that are plentiful of n-3 PUFAs can bring benefits in the treatment of osteoarthritis. Previously two phase I human studies based on in vitro transfer of the cDNA via lentivirus to arthritic joints have confirmed its feasibility and safety in human subjects. Consequently, we hypothesis that directly infect the chondrocytes and synoviocytes with lentivirus carrying the fat-1 gene could be a well therapeutic strategy for OA in humans.
authors.affiliation: Department of Orthopaedic, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510665, Guangdong, PR China.
authors.forename: Min-jun
authors.initials: MJ
authors.lastname: Huang
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Xiao-chen
authors.initials: XC
authors.lastname: Zheng
authors.forename: Zhong-min
authors.initials: ZM
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Yan
authors.forename: Tian-yu
authors.initials: TY
authors.lastname: Chen
authors.forename: Xiao-chun
authors.initials: XC
authors.lastname: Bai
authors.forename: Da-di
authors.initials: DD
authors.lastname: Jin
mesh_terms: D015820:Cadherins / Q000235:genetics*; D015316:Genetic Therapy; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D010003:Osteoarthritis / Q000235:genetics / Q000517:prevention & control*
chemical_list: D015820:Cadherins; C502403:FAT1 protein, human