Initial displacement of the intra-articular surface after articular fracture correlates with PTA in C57BL/6 mice but not "superhealer" MRL/MpJ mice.
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2021-09
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Abstract
Posttraumatic arthritis (PTA) occurs commonly after articular fracture and may arise, in part, from joint surface incongruity after injury. MRL/MpJ (MRL) "super-healer" mice are protected from PTA compared to C57BL/6 (B6) mice following articular fracture. However, the relationship between the initial displacement of the articular surface, biologic response, and susceptibility to PTA after fracture remains unclear. The objective of this study was to assess whether joint incongruity after articular fracture, as measured by in vivo micro-computed tomography (microCT), could predict pathomechanisms of PTA in mice. B6 and MRL mice (n = 12/strain) received a closed articular fracture (fx) of the left tibial plateau. Articular incongruity was quantified as bone surface deviations (BSD) for each in vivo microCT scan obtained from pre-fx to 8 weeks post-fx, followed by histologic assessment of arthritis. Serum concentrations of bone formation (PINP) and bone resorption (CTX-I) biomarkers were quantified longitudinally. Both strains showed increases in surface incongruity over time, as measured by increases in BSD. In B6 mice, acute surface incongruity was significantly correlated to the severity of PTA (R 2 = 0.988; p = .0006), but not in MRL mice (R 2 = 0.224; p = .220). PINP concentrations significantly decreased immediately post-fx in B6 mice (p = .023) but not in MRL mice, indicating higher bone synthesis in MRL mice. MRL/MpJ mice demonstrate a unique biologic response to articular fracture such that the observed articular bone surface displacement does not correlate with the severity of subsequent PTA. Clinical Relevance: Identifying therapies to enhance acute biologic repair following articular fracture may mitigate the risk of articular surface displacement for PTA.
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Vovos, Tyler J, Bridgette D Furman, Janet L Huebner, Kelly A Kimmerling, Gangadhar M Utturkar, Cynthia L Green, Virginia B Kraus, Farshid Guilak, et al. (2021). Initial displacement of the intra-articular surface after articular fracture correlates with PTA in C57BL/6 mice but not "superhealer" MRL/MpJ mice. Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 39(9). pp. 1977–1987. 10.1002/jor.24912 Retrieved from https://hdl.handle.net/10161/24548.
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Scholars@Duke
![Green](https://scholars.duke.edu/profile-images/thumbnail200/0023817.jpg)
Cynthia Lea Green
Survival Analysis
Longitudinal Data Analysis
Logistic Regression
Missing Data
Clinical Trial Methods
Maximum Likelihood Methods
![Kraus](https://scholars.duke.edu/profile-images/thumbnail200/0078823.jpg)
Virginia Byers Kraus
Virginia Byers Kraus, MD, PhD, is the Mary Bernheim Distinguished Professor of Medicine, Professor of Orthopaedic Surgery, Professor of Pathology and a faculty member of the Duke Molecular Physiology Institute in the Duke University School of Medicine. She is a practicing Rheumatologist with over 30 years’ experience in translational musculoskeletal research focusing on osteoarthritis, the most common of all arthritides. She trained at Brown University (ScB 1979), Duke University (MD 1982, PhD 1993) and the Duke University School of Medicine (Residency in Internal Medicine and Fellowship in Rheumatology). Her career has focused on elucidating osteoarthritis pathogenesis and translational research into the discovery and validation of biomarkers for early osteoarthritis detection, prediction of progression, monitoring of disease status, and facilitation of therapeutic developments. She is co-PI of the Foundation for NIH Biomarkers Consortium Osteoarthritis project. Trained as a molecular biologist and a Rheumatologist, she endeavors to study disease from bedside to bench.
![Olson](https://scholars.duke.edu/profile-images/thumbnail200/0272047.jpg)
Steven Arthur Olson
As an Orthopedic Surgeon my primary focus of research is joint preservation. My primary clinical interests are Orthopedic Trauma and Hip Reconstruction.
In Orthopedic Trauma my research interests are 1) Basic science investigations of articular fractures with two current animal models in use. 2) Clinical research includes evaluation of techniques to reduce and stabilize articular fractures, as well as management of open fractures.
In the area of Hip Reconstruction my areas of research are 1) Hip Arthroscopy and treatment of hip disorders, and treatment of labral tears in the treatment of hip pain. 2) Periacetabular osteotomy for the treatment of hip dysplasia.
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