Abstract
The epiphyseal growth plate is a developmental region responsible for linear bone growth, in which chondrocytes undertake a tightly regulated series of biological processes. Concomitant with the cessation of growth and sexual maturation, the human growth plate undergoes progressive narrowing, and ultimately disappears. Despite the crucial role of this growth plate fusion “bridging” event, the precise mechanisms by which it is governed are complex and yet to be established. Progress is hindered by the current methods for growth plate visualization; these are invasive and largely rely on histological procedures. Here, we describe our non-invasive method utilizing synchrotron X-ray computed microtomography for the examination of growth plate bridging, which ultimately leads to its closure coincident with termination of further longitudinal bone growth. We then apply this method to a dataset obtained from a benchtop micro computed tomography scanner to highlight its potential for wide usage. Furthermore, we conduct finite element modeling at the micron-scale to reveal the effects of growth plate bridging on local tissue mechanics. Employment of these 3D analyses of growth plate bone bridging is likely to advance our understanding of the physiological mechanisms that control growth plate fusion.
Highlights
Endochondral ossification is a tightly regulated process responsible for the formation and postnatal linear growth of the long bones, including the tibia and femur
We used our method for the visualization and quantification of growth plate bridging, and our finite element (FE) model to examine the effects of bridging on local tissue mechanics
The results presented in this study report a method for the 3D quantification of growth plate bridging in murine bones
Summary
Endochondral ossification is a tightly regulated process responsible for the formation and postnatal linear growth of the long bones, including the tibia and femur. The growth plate consists of chondrocytes arranged in columns These chondrocytes are surrounded by their extracellular matrix, consisting of specific collagens, namely Collagen types II and X, as well as proteoglycans such as aggrecan and other non-collagenous matrix proteins including the SIBLING family of proteins (Ballock and O’Keefe, 2003; Mackie et al, 2011). Chondrocytes undergo distinct maturation stages of proliferation, differentiation, and hypertrophy, while maintaining their spatially fixed location (Hunziker et al, 1987). It is the terminally differentiated hypertrophic chondrocyte, which mineralizes its surrounding extracellular matrix (Castagnola et al, 1988).
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