Novel model for the induction of postnatal murine hip deformity

Abstract

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.

Exploring infant hip position and muscle activity in common baby gear and orthopedic devices

“…14 The latter was also established in recent murine models, where decreased gluteal and quadriceps muscle loading resulted in altered postnatal bone and joint shape and growth, meaning that inactive lower-extremity muscles may contribute to the development or aggravation of DDH in neonates. 15,16 Murine models also show that restrictive leg positioning, specifically straight-leg swaddling, increased the prevalence of DDH compared to no restriction on leg positioning. 18 This finding is also apparent in anthropologic studies of populations where tight, straight-leg swaddling has been widely practiced historically, with such swaddling being identified as a likely contributor to the high prevalence of DDH in these populations.…”

“…14 Additionally, recent murine studies suggest that decreased gluteal and quadriceps muscle loading resulted in altered postnatal bone and joint shape and growth, meaning that inactive lower-extremity muscles may contribute to the development or aggravation of DDH in neonates. 15,16 Human infants, particularly in the first 6 months of life, are at a risk of developing or exacerbating DDH if their hips are immobilized for prolonged periods of time through tight straight-leg swaddling, 17 a finding which has been supported in murine models. 18 Yet, the role of inactive or active muscles to promote hip development in human infants has not been studied.…”

The surgical destabilization of the abductor muscle leads to development of instability-associated hip osteoarthritis in mice

“…Currently, only a few rodent hip OA models have been established. These models can be generally categorized as either chemically or surgically induced OA [ 20 , 28 ]. Intra-articular injection of monosodium iodoacetate (a chondrocyte glycolytic inhibitor) triggered rapid hip OA development compared to controls within 14 days in a rat model.…”

“…However, it is not clear whether such a progressive and destructive OA phenotype represents chronic human hip OA. In another study, various degrees of hip instability—mild, moderate, severe and FH resection—were surgically induced in mice at weaning (3-weeks-old neonatal pups) [ 20 ]. These data suggest that progressive hip instability resulting from periarticular soft tissue insufficiency led to morphometric changes in the growing mouse hip.…”

“…Despite these benefits, large animals are not amenable to genetic modification to better define the cellular and molecular mechanisms of pathogenesis, as can be conducted in mice [ 19 ]. Furthermore, there is a paucity of literature on murine hip injury models [ 20 ]. The purpose of the present study was to establish a novel murine model of instability-associated hip OA induced by abductor injury.…”