Effects of knockout of the receptor for advanced glycation end-products on bone mineral density and synovitis in mice with intra-articular fractures
| Autor: | Dongrim, Seol, Yuki, Tochigi, Ashley M, Bogner, Ino, Song, Douglas C, Fredericks, Gail L, Kurriger, Sonja M, Smith, Jessica E, Goetz, Joseph A, Buckwalter, James A, Martin |
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| Rok vydání: | 2017 |
| Předmět: |
Cartilage
Articular Male Mice Knockout Synovitis Intra-Articular Fractures Receptor for Advanced Glycation End Products X-Ray Microtomography Article Mice Inbred C57BL Tibial Fractures Disease Models Animal Mice Bone Density Matrix Metalloproteinase 13 Osteoarthritis Animals Matrix Metalloproteinase 3 |
| Zdroj: | Journal of orthopaedic research : official publication of the Orthopaedic Research Society. 36(9) |
| ISSN: | 1554-527X |
| Popis: | Our group employed the mouse closed intra-articular fracture (IAF) model to test the hypothesis that the innate immune system plays a role in initiating synovitis and post-traumatic osteoarthritis (PTOA) in fractured joints. A transgenic strategy featuring knockout of the receptor for advanced glycation end-products (RAGE(−/−)) was pursued. The 42 and 84 mJ impacts used to create fractures were in the range previously reported to cause PTOA at 60 days post-fracture. MicroCT (μCT) was used to assess fracture patterns and epiphyseal and metaphyseal bone loss at 30 and 60 days post-fracture. Cartilage degeneration, synovitis, and matrix metalloproteinase (MMP-3, −13) expression were evaluated by histologic analyses. In wild-type mice, μCT imaging showed that 84 mJ impacts led to significant bone loss at 30 days (p < 0.05), but recovered to normal at 60 days. Bone losses did not occur in RAGE(−/−) mice. Synovitis was significantly elevated in 84 mJ impact wild-type mice at both endpoints (30 day, p = 0.001; 60 day, p = 0.05), whereas in RAGE(−/−) mice synovitis was elevated only at 30 days (p = 0.02). Mankin scores were slightly elevated in both mouse strains at 30 days, but not at 60 days. Immunohistochemistry revealed significant fracture-related increases in MMP-3 and −13 expression at 30 days (p < 0.05), with no significant difference between genotypes. These findings indicated that while RAGE(−/−) accelerated recovery from fracture and diminished synovitis, arthritic changes were temporary and too modest to detect an effect on the pathogenesis of PTOA. |
| Databáze: | OpenAIRE |
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