Journal article
Complementary models reveal cellular responses to contact stresses that contribute to post-traumatic osteoarthritis
Journal of orthopaedic research, Vol.35(3), pp.515-523
03/2017
DOI: 10.1002/jor.23389
PMCID: PMC5303196
PMID: 27509320
Abstract
Two categories of joint overloading cause post-traumatic osteoarthritis (PTOA): single acute traumatic loads/impactions and repetitive overloading due to incongruity/instability. We developed and refined three classes of complementary models to define relationships between joint overloading and progressive cartilage loss across the spectrum of acute injuries and chronic joint abnormalities: explant and whole joint models that allow probing of cellular responses to mechanical injury and contact stresses, animal models that enable study of PTOA pathways in living joints and pre-clinical testing of treatments, and patient-specific computational models that define the overloading that causes OA in humans. We coordinated methodologies across models so that results from each informed the others, maximizing the benefit of this complementary approach. We are incorporating results from these investigations into biomathematical models to provide predictions of PTOA risk and guide treatment. Each approach has limitations, but each provides opportunities to elucidate PTOA pathogenesis. Taken together, they help define levels of joint overloading that cause cartilage destruction, show that both forms of overloading can act through the same biologic pathways, and create a framework for initiating clinical interventions that decrease PTOA risk. Considered collectively, studies extending from explants to humans show that thresholds of joint overloading that cause cartilage loss can be defined, that to at least some extent both forms of joint overloading act through the same biologic pathways, and interventions that interrupt these pathways prevent cartilage damage. These observations suggest that treatments that decrease the risk of all forms of OA progression can be discovered. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:515-523, 2017.
Details
- Title: Subtitle
- Complementary models reveal cellular responses to contact stresses that contribute to post-traumatic osteoarthritis
- Creators
- James A Martin - Department of Biomedical Engineering, University of Iowa, Iowa City, IowaDonald D Anderson - Department of Biomedical Engineering, University of Iowa, Iowa City, IowaJessica E Goetz - Department of Biomedical Engineering, University of Iowa, Iowa City, IowaDouglas Fredericks - Department of Orthopedics and Rehabilitation, University of Iowa, 2181 Westlawn Building, Iowa City 52242, IowaDouglas R Pedersen - Department of Biomedical Engineering, University of Iowa, Iowa City, IowaBruce P Ayati - Department of Mathematics, University of Iowa, Iowa City, IowaJ Lawrence Marsh - Department of Orthopedics and Rehabilitation, University of Iowa, 2181 Westlawn Building, Iowa City 52242, IowaJoseph A Buckwalter - Iowa City Veterans Administration Medical Center, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of orthopaedic research, Vol.35(3), pp.515-523
- DOI
- 10.1002/jor.23389
- PMID
- 27509320
- PMCID
- PMC5303196
- NLM abbreviation
- J Orthop Res
- ISSN
- 1554-527X
- eISSN
- 1554-527X
- Publisher
- United States
- Grant note
- P50 AR048939 / NIAMS NIH HHS P50 AR055533 / NIAMS NIH HHS
- Language
- English
- Date published
- 03/2017
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Stead Family Department of Pediatrics; Pharmaceutical Sciences and Experimental Therapeutics; Orthopedics and Rehabilitation; Industrial and Systems Engineering; Craniofacial Anomalies Research Center; Injury Prevention Research Center; Mathematics
- Record Identifier
- 9983985718002771
Metrics
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