Journal article
Effects of knockout of the receptor for advanced glycation end-products on bone mineral density and synovitis in mice with intra-articular fractures
Journal of orthopaedic research, Vol.36(9), pp.2439-2449
09/2018
DOI: 10.1002/jor.24021
PMCID: PMC6128287
PMID: 29667227
Abstract
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. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2439-2449, 2018.
Details
- Title: Subtitle
- Effects of knockout of the receptor for advanced glycation end-products on bone mineral density and synovitis in mice with intra-articular fractures
- Creators
- Dongrim Seol - Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, IA 52242Yuki Tochigi - Department of Orthopaedic Surgery, Dokkyo Medical University Koshigaya Hospital, Saitama, JapanAshley M Bogner - Bone Healing Research Laboratory and Iowa Spine Research Laboratory, University of Iowa, Coralville, IA 52241Ino Song - Department of Biomedical Engineering, University of Iowa, Iowa City, IA 52242Douglas C Fredericks - Bone Healing Research Laboratory and Iowa Spine Research Laboratory, University of Iowa, Coralville, IA 52241Gail L Kurriger - Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, IA 52242Sonja M Smith - Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, IA 52242Jessica E Goetz - Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, IA 52242Joseph A Buckwalter - Veterans Affairs Medical Center, Iowa City, IA 52246James A Martin - Department of Biomedical Engineering, University of Iowa, Iowa City, IA 52242
- Resource Type
- Journal article
- Publication Details
- Journal of orthopaedic research, Vol.36(9), pp.2439-2449
- DOI
- 10.1002/jor.24021
- PMID
- 29667227
- PMCID
- PMC6128287
- NLM abbreviation
- J Orthop Res
- ISSN
- 0736-0266
- eISSN
- 1554-527X
- Publisher
- United States
- Grant note
- NIH NIAMS P50 AR055533 / NIAMS NIH HHS Iowa Department of Orthopedics and Rehabilitation
- Language
- English
- Date published
- 09/2018
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Orthodontics; Stead Family Department of Pediatrics; Pharmaceutical Sciences and Experimental Therapeutics; Orthopedics and Rehabilitation; Craniofacial Anomalies Research Center; Injury Prevention Research Center; Biochemistry and Molecular Biology
- Record Identifier
- 9984040349402771
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