TY - JOUR
T1 - Initial displacement of the intra-articular surface after articular fracture correlates with PTA in C57BL/6 mice but not “superhealer” MRL/MpJ mice
AU - Vovos, Tyler J.
AU - Furman, Bridgette D.
AU - Huebner, Janet L.
AU - Kimmerling, Kelly A.
AU - Utturkar, Gangadhar M.
AU - Green, Cynthia L.
AU - Kraus, Virginia B.
AU - Guilak, Farshid
AU - Olson, Steven A.
N1 - Funding Information:
The authors would like to acknowledge Dr. Louis DeFrate for his expertise and assistance in analysis of computed tomography images, Steve Johnson, RVT, for his technical assistance with animal experiments, and Dr. Holly Leddy for her assistance with histological grading and statistical analysis.?The funding for?this study was provided by the Department of Defense Translational Research Partnership Awards W81XWH-12-1-0621, W81XWH-12-1-0622, and W81XWH-12-1-0623, the Arthritis Foundation, and NIH Equipment Grant S10-OD010707.
Publisher Copyright:
© 2020 Orthopaedic Research Society. Published by Wiley Periodicals LLC
PY - 2021/9
Y1 - 2021/9
N2 - 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.
AB - 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.
KW - arthritis
KW - biomarkers
KW - joint incongruity
KW - knee fracture
KW - trauma
UR - http://www.scopus.com/inward/record.url?scp=85097272111&partnerID=8YFLogxK
U2 - 10.1002/jor.24912
DO - 10.1002/jor.24912
M3 - Article
C2 - 33179316
AN - SCOPUS:85097272111
VL - 39
SP - 1977
EP - 1987
JO - Journal of Orthopaedic Research
JF - Journal of Orthopaedic Research
SN - 0736-0266
IS - 9
ER -