TY - JOUR
T1 - Novel model for the induction of postnatal murine hip deformity
AU - Killian, Megan L.
AU - Locke, Ryan C.
AU - James, Michael G.
AU - Atkins, Penny R.
AU - Anderson, Andrew E.
AU - Clohisy, John C.
N1 - Funding Information:
Grant sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases; Grant number: NIH P30 AR057235; Grant sponsor: National Institute of Biomedical Imaging and Bioengineering; Grant number: R01-EB016701; Grant sponsor: National Institute of General Medical Sciences; Grant numbers: P41-GM103545, R01-GM083925. Correspondence to: Megan L. Killian (T: + 1 302 257-1913; F: 302-831-8179; E-mail: killianm@udel.edu)
Funding Information:
Special thanks to Patrick Canning (University of Delaware) for assistance with dynamic histomorphometry and histological imaging and Daniel Leib (Washington University) for assistance with microCT image processing. This research was supported by the Washington University Musculoskeletal Research Center (NIH P30 AR057235) and the National Institute of General Medical Sciences of the National Institutes of Health (P41-GM103545, R01-GM083925, and R01-EB016701).
Publisher Copyright:
© 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
PY - 2019/1
Y1 - 2019/1
N2 - Acetabular dysplasia is a common, multi-etiological, pre-osteoarthritic (OA) feature that can lead to pain and instability of the young adult hip. Despite the clinical significance of acetabular dysplasia, there is a paucity of small animal models to investigate structural and functional changes that mediate morphology of the dysplastic hip and drive the subsequent OA cascade. Utilizing a novel murine model developed in our laboratory, this study investigated the role of surgically induced unilateral instability of the postnatal hip on the initiation and progression of acetabular dysplasia and impingement up to 8-weeks post-injury. C57BL6 mice were used to develop titrated levels of hip instability (i.e., mild, moderate, and severe instabillity or femoral head resection) at weaning. Joint shape, acetabular coverage, histomorphology, and statistical shape modeling were used to assess quality of the hip following 8 weeks of destabilization. Acetabular coverage was reduced following severe, but not moderate, instability. Moderate instability induced lateralization of the femur without dislocation, whereas severe instability led to complete dislocation and pseudoacetabulae formation. Mild instability did not result in morphological changes to the hip. Removal of the femoral head led to reduced hip joint space volume. These data support the notion that hip instability, driven by mechanical loss-of-function of soft connective tissue, can induce morphometric changes in the growing mouse hip. This work developed a new mouse model to study hip health in the murine adolescent hip and is a useful tool for investigating the mechanical and structural adaptations to hip instability during growth.
AB - Acetabular dysplasia is a common, multi-etiological, pre-osteoarthritic (OA) feature that can lead to pain and instability of the young adult hip. Despite the clinical significance of acetabular dysplasia, there is a paucity of small animal models to investigate structural and functional changes that mediate morphology of the dysplastic hip and drive the subsequent OA cascade. Utilizing a novel murine model developed in our laboratory, this study investigated the role of surgically induced unilateral instability of the postnatal hip on the initiation and progression of acetabular dysplasia and impingement up to 8-weeks post-injury. C57BL6 mice were used to develop titrated levels of hip instability (i.e., mild, moderate, and severe instabillity or femoral head resection) at weaning. Joint shape, acetabular coverage, histomorphology, and statistical shape modeling were used to assess quality of the hip following 8 weeks of destabilization. Acetabular coverage was reduced following severe, but not moderate, instability. Moderate instability induced lateralization of the femur without dislocation, whereas severe instability led to complete dislocation and pseudoacetabulae formation. Mild instability did not result in morphological changes to the hip. Removal of the femoral head led to reduced hip joint space volume. These data support the notion that hip instability, driven by mechanical loss-of-function of soft connective tissue, can induce morphometric changes in the growing mouse hip. This work developed a new mouse model to study hip health in the murine adolescent hip and is a useful tool for investigating the mechanical and structural adaptations to hip instability during growth.
KW - acetabular dysplasia
KW - femoroacetabular joint
KW - impingement
KW - postnatal growth
KW - statistical shape modeling
UR - http://www.scopus.com/inward/record.url?scp=85056760488&partnerID=8YFLogxK
U2 - 10.1002/jor.24146
DO - 10.1002/jor.24146
M3 - Article
C2 - 30259572
AN - SCOPUS:85056760488
SN - 0736-0266
VL - 37
SP - 151
EP - 160
JO - Journal of Orthopaedic Research
JF - Journal of Orthopaedic Research
IS - 1
ER -