title: Adenovirus-mediated osteoprotegerin ameliorates cartilage destruction by inhibiting proteoglycan loss and chondrocyte apoptosis in rats with collagen-induced arthritis.
abstract: Our aim is to elucidate the effects of osteoproteogerin (OPG) on cartilage destruction in rats as a model of collagen-induced arthritis (CIA). To establish the CIA model, Sprague Dawley rats were injected with bovine type II collagen solution subcutaneously via the tails. Adenovirus-mediated OPG (Ad-OPG) was then injected intra-articularly either at the beginning of CIA (early OPG treatment) or one week after CIA establishment (late OPG treatment); vehicle or Ad-green fluorescent protein were injected as controls. The rats were killed 4 weeks after treatment. Ankle-joint sections were obtained for histology. Serum samples were collected for enzyme-linked immunosorbent assay. Safranin O staining showed that proteoglycan loss was inhibited in the early and late Ad-OPG groups. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining revealed that both early and late Ad-OPG treatments significantly prevented chondrocyte apoptosis in CIA rats. Furthermore, disintegrin and metalloproteinase with thrombospondin motif-5 expression decreased remarkably in the early and late OPG treatment groups. However, the cartilage destruction score, cartilage oligomeric matrix protein level and caspase-3 expression were only decreased in the early Ad-OPG treatment group. Additionally, ankle-joint swelling and the interleukin-1β expression level in CIA rats were not notably altered by Ad-OPG treatment. Taken together, our results suggest that early Ad-OPG treatment has potent protective effects against cartilage destruction during rheumatoid arthritis progression, mainly by reducing proteoglycan loss and chondrocyte apoptosis.
authors.affiliation: Spine Lab, Department of Orthopedic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China, 310003.
authors.forename: Zhi-yun
authors.initials: ZY
authors.lastname: Feng
authors.affiliation: Department of Orthopedics, Beilun People's Hospital, No. 1288, Lu shan Road, Ningbo, Zhejiang Province, People's Republic of China, 315806.
authors.forename: Zhen-nian
authors.initials: ZN
authors.lastname: He
authors.affiliation: Department of Orthopedics, Beilun People's Hospital, No. 1288, Lu shan Road, Ningbo, Zhejiang Province, People's Republic of China, 315806.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Center, Beilun People's Hospital, No. 1288, Lu shan Road, Ningbo, Zhejiang Province, People's Republic of China, 315806.
authors.forename: Yi-qiao
authors.initials: YQ
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Beilun People's Hospital, No. 1288, Lu shan Road, Ningbo, Zhejiang Province, People's Republic of China, 315806.
authors.forename: Jian
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Orthopedics, Beilun People's Hospital, No. 1288, Lu shan Road, Ningbo, Zhejiang Province, People's Republic of China, 315806.
authors.forename: Yuan-lin
authors.initials: YL
authors.lastname: Xu
authors.affiliation: Department of Orthopedics, Beilun People's Hospital, No. 1288, Lu shan Road, Ningbo, Zhejiang Province, People's Republic of China, 315806.
authors.forename: Ming-yuan
authors.initials: MY
authors.lastname: Han
authors.affiliation: Spine Lab, Department of Orthopedic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China, 310003. chenzhongzju@gmail.com.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000256:Adenoviridae / Q000378:metabolism*; D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism*; D019902:Chondrocytes / Q000378:metabolism*; D024043:Collagen Type II / Q000378:metabolism*; D053244:Osteoprotegerin / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D024043:Collagen Type II; D053244:Osteoprotegerin; D011509:Proteoglycans
keywords: Cartilage destruction; Chondrocyte apoptosis; Collagen-induced arthritis; Osteoprotegerin; Proteoglycan loss; Rat (Sprague Dawley)