Journal article
Time-dependent loss of mitochondrial function precedes progressive histologic cartilage degeneration in a rabbit meniscal destabilization model
Journal of orthopaedic research, Vol.35(3), pp.590-599
03/2017
DOI: 10.1002/jor.23327
PMCID: PMC5148713
PMID: 27279147
Abstract
The goals of this work were to characterize progression of osteoarthritic cartilage degeneration in a rabbit medial meniscus destabilization (MMD) model and then to use the model to identify pre-histologic disruptions in chondrocyte metabolism under chronically elevated joint contact stresses in vivo. To characterize PTOA progression, 24 rabbits received either MMD or sham surgery. Limb loading was analyzed preoperatively and at regular postoperative intervals using a Tekscan pressure-sensitive walkway. Animals were euthanized 8 (n = 8 MMD; n = 8 sham) or 26 weeks (n = 8 MMD) postoperatively for histological cartilage evaluation by an objective, semi-automated Mankin scoring routine. To examine pre-histologic pathology, MMD was performed on an additional 20 rabbits, euthanized 1 (n = 9) or 4 weeks (n = 10) postoperatively. Chondrocytes were harvested fresh for measurement of mitochondrial function, an intracellular indicator of pathology after mechanical injury. Both MMD and sham surgery caused slight decreases in limb loading which returned to preoperative levels after 2 weeks. Histologically apparent cartilage damage progressed from 8 to 26 weeks after MMD. Changes in chondrocyte respiration were variable at 1 week, but by 4 weeks postoperatively chondrocyte mitochondrial function was significantly reduced. Many human injuries that lead to PTOA are relatively mild, and the cell-level mechanisms leading to disease remain unclear. We have documented PTOA progression in an animal model of subtle joint injury under continued use, and demonstrated that this model provides a realistic environment for investigation of multi-stage cellular pathology that develops prior to overt tissue degeneration and which could be targeted for disease modifying treatments. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:590-599, 2017.
Details
- Title: Subtitle
- Time-dependent loss of mitochondrial function precedes progressive histologic cartilage degeneration in a rabbit meniscal destabilization model
- Creators
- Jessica E Goetz - Department of Biomedical Engineering, University of Iowa, Iowa City, IowaMitchell C Coleman - Department of Orthopaedics and Rehabilitation, Orthopaedic Biomechanics Lab, University of Iowa, 2180 Westlawn Building, Iowa City, Iowa, 52242-110Douglas C Fredericks - Department of Orthopaedics and Rehabilitation, Orthopaedic Biomechanics Lab, University of Iowa, 2180 Westlawn Building, Iowa City, Iowa, 52242-110Emily Petersen - Department of Orthopaedics and Rehabilitation, Orthopaedic Biomechanics Lab, University of Iowa, 2180 Westlawn Building, Iowa City, Iowa, 52242-110James A Martin - Department of Biomedical Engineering, University of Iowa, Iowa City, IowaTodd O McKinley - Department of Orthopaedics, Indiana University Methodist Hospital, Indianapolis, IndianaYuki Tochigi - Department of Orthopaedics, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Saitama, Japan
- Resource Type
- Journal article
- Publication Details
- Journal of orthopaedic research, Vol.35(3), pp.590-599
- DOI
- 10.1002/jor.23327
- PMID
- 27279147
- PMCID
- PMC5148713
- NLM abbreviation
- J Orthop Res
- ISSN
- 0736-0266
- eISSN
- 1554-527X
- Publisher
- United States
- Grant note
- P50 AR055533 / NIAMS NIH HHS
- Language
- English
- Date published
- 03/2017
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics; Orthopedics and Rehabilitation; Radiation Oncology; Craniofacial Anomalies Research Center
- Record Identifier
- 9984040292002771
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