Treatment of collagenase-induced osteoarthritis with a viral vector encoding TSG-6 results in ectopic bone formation

PeerJ

article

Mathijs G.A. Broeren¹  Irene Di Ceglie¹  Miranda B. Bennink¹  Peter L.E.M. van Lent¹  Wim B. van den Berg¹  Marije I. Koenders¹  Esmeralda N. Blaney Davidson¹  Peter M. van der Kraan¹  Fons A.J. van de Loo¹ 

[1] Experimental Rheumatology, Radboud University Medical Center

关键词: TSG-6;    Osteoclasts;    Gene therapy;    Osteoarthritis;   

DOI  :  10.7717/peerj.4771

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

Objective Tumor necrosis factor-inducible gene 6 (TSG-6) has anti-inflammatory and chondroprotective effects in mouse models of inflammatory arthritis. Because cartilage damage and inflammation are also observed in osteoarthritis (OA), we determined the effect of viral overexpression of TSG-6 in experimental osteoarthritis. Methods Bone marrow-derived cells were differentiated to multinucleated osteoclasts in the presence of recombinant TSG-6 or after transduction with a lentiviral TSG-6 expression vector. Multi-nucleated osteoclasts were analyzed after tartrate resistant acid phosphatase staining and resorption activity was determined on dentin slices. Collagenase-induced osteoarthritis (CIOA) was induced in C57BL/6 mice after intra-articular injection of an adenoviral TSG-6 or control luciferase expression vector. Inflammation-related protease activity was measured using bioluminescent Prosense probes. After a second adenovirus injection, cartilage damage was assessed in histological sections stained with Safranin-O. Ectopic bone formation was scored in X-ray images of the affected knees. Results TSG-6 did not inhibit the formation of multi-nucleated osteoclasts, but caused a significant reduction in the resorption activity on dentin slices. Adenoviral TSG-6 gene therapy in CIOA could not reduce the cartilage damage compared to the luciferase control virus and no significant difference in inflammation-related protease activity was noted between the TSG-6 and control treated group. Instead, X-ray analysis and histological analysis revealed the presence of ectopic bone formation in the TSG-6 treated group. Conclusion Gene therapy based on the expression of TSG-6 could not provide cartilage protection in experimental osteoarthritis, but instead resulted in increased ectopic bone formation.

【 授权许可】

CC BY