Resources / Publications
Daniel J. Buss (1), Natalie Reznikov (2), Marc D. McKee (3)
Journal of Structural Biology, August 2020. DOI: 10.1016/j.jsb.2020.107603
Bone, mineralization, X-linked hypophosphatemia (XLH), Hyp mice, osteocyte, mineral tessellation
In bone, structural components such as mineral extend across length scales to provide essential biomechanical functions. Using X-ray micro-computed tomography (µCT), and focused-ion beam scanning electron microscopy (FIB-SEM) in serial-surface-view mode, together with 3D reconstruction, entire mouse skeletons and small bone tissue volumes were examined in normal wildtype (WT) and mutant Hyp mice (an animal model for X-linked hypophosphatemia/XLH, a disease with severe hypomineralization of bone). 3D thickness maps of the skeletons showed pronounced irregular thickening and abnormalities of many skeletal elements in Hyp mice compared to WT mice. At the micro- and nanoscale, near the mineralization front in WT tibial bone volumes, mineralization foci grow as expanding prolate ellipsoids to abut and pack against one another to form a congruent and contiguous mineral tessellation pattern within collagen bundles that contributes to lamellar periodicity. In the osteomalacic Hyp mouse bone, mineralization foci form and begin initial ellipsoid growth within normally organized collagen assembly, but their growth trajectory aborts. Mineralization-inhibiting events in XLH/Hyp (low circulating serum phosphate, and increased matrix osteopontin) combine to result in decreased mineral ellipsoid tessellation – a defective mineral-packing organization that leaves discrete mineral volumes isolated in the extracellular matrix such that ellipsoid packing/tessellation is not achieved. Such a severely altered mineralization pattern invariably leads to abnormal compliance, other aberrant biomechanical properties, and altered remodeling of bone, all of which indubitably lead to macroscopic bone deformities and anomalous mechanical performance in XLH/Hyp. Also, we show the relationship of osteocytes and their cell processes to this mineralization pattern.
(1) Department of Anatomy and Cell Biology, McGill University, 3640 University Street, Montreal, Quebec H3A 0C7, Canada.
(2) Object Research Systems Inc., Object Research Systems, 760 Saint Paul West, Montreal, Quebec H3C 1M4, Canada.
(3) Faculty of Dentistry, McGill University, 3640 University Street, Montreal, Quebec H3A 0C7, Canada.
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