Local Changes to the Distal Femoral Growth Plate Following Injury in Mice

Abstract

Injury to the growth plate is associated with growth disturbances, most notably premature cessation of growth. The goal of this study was to identify spatial changes in the structure and composition of the growth plate in response to injury to provide a foundation for developing therapies that minimize the consequences for skeletal development. We used contrast-enhanced microcomputed tomography (CECT) and histological analyses of a murine model of growth plate injury to quantify changes in the cartilaginous and osseous tissue of the growth plate. To distinguish between local and global changes, the growth plate was divided into regions of interest near to and far from the injury site. We noted increased thickness and CECT attenuation (a measure correlated with glycosaminoglycan (GAG) content) near the injury, and increased tissue mineral density (TMD) of bone bridges within the injury site, compared to outside the injury site and contralateral growth plates. Furthermore, we noted disruption of the normal zonal organization of the physis. The height of the hypertrophic zone was increased at the injury site, and the relative height of the proliferative zone was decreased across the entire injured growth plate. These results indicate that growth plate injury leads to localized disruption of cellular activity and of endochondral ossification. These local changes in tissue structure and composition may contribute to the observed retardation in femur growth. In particular, the changes in proliferative and hypertrophic zone heights seen following injury may impact growth and could be targeted when developing therapies for growth plate injury.

Analysis of Association between Morphometric Parameters of Growth Plate and Bone Growth of Tibia in Mice and Humans

“…31 Researchers frequently use wild type or transgenic mice to study orthopedic conditions. [32][33][34][35][36][37] Histological features are a gold standard to provide evidence of growth plate dysfunction. There are various parameters to evaluate abnormalities of the growth plate structure, including total height, zone height, cell density, and zone proportion.…”

A FoxA2+ long-term stem cell population is necessary for growth plate cartilage regeneration after injury

“…Salter–Harris classification system divides GP fractures into five groups predicated on fracture morphology involving the physis ± epiphysis and/or metaphysis and the deleterious effect on appendicular growth 3 . Salter–Harris fractures through the physis often result in the formation of a “bony bar” bridging the epiphysis to the metaphysis 32 – 34 . In contrast, Salter–Harris type1 fractures where the cleavage plane is along the GP, preserving the RZ, heal without significant growth disturbance 3 , 4 .…”

Enlightenment of Growth Plate Regeneration Based on Cartilage Repair Theory: A Review

“…As more hypertrophic chondrocytes occurred after the fibrogenic phase, the height of resting zone and hypertrophic zone increased while proliferative zone height relatively reduced. Immunohistochemistry of Col X staining also reported that Col X extends throughout the entire injury site (Drenkard et al, 2017). Furthermore, the GP injury also affects the adjacent non-injured region because injuries destroyed the controlled endochondral ossification process.…”