Resumen de A distinctive patchy osteomalacia characterises Phospho1-deficient mice
Alan Boyde, Katherine A. Staines, Behzad Javaheri, Jose Luis Millan, A. A. Pitsillides, Colin Farquharson
The phosphatase PHOSPHO1 is involved in the initiation of biomineralisation. Bones in Phospho1 knockout (KO)mice show histological osteomalacia with frequent bowing of long bones and spontaneous fractures: they containless mineral, with smaller mineral crystals. However, the consequences of Phospho1 ablation on the microscalestructure of bone are not yet fully elucidated. Tibias and femurs obtained from wild-type and Phospho1 null (KO)mice (25–32 weeks old) were embedded in PMMA, cut and polished to produce near longitudinal sections. Blocksurfaces were studied using 20 kV backscattered-electron (BSE) imaging, and again after iodine staining to revealnon-mineralised matrix and cellular components. For 3D characterisation, we used X-ray micro-tomography.Bones opened with carbide milling tools to expose endosteal surfaces were macerated using an alkaline bacterialpronase enzyme detergent, 5% hydrogen peroxide and 7% sodium hypochlorite solutions to produce 3D surfacesfor study with 3D BSE scanning electron microscopy (SEM). Extensive regions of both compact cortical andtrabecular bone matrix in Phospho1 KO mice contained no significant mineral and/or showed arrestedmineralisation fronts, characterised by a failure in the fusion of the calcospherite-like, separately mineralising,individual micro-volumes within bone. Osteoclastic resorption of the uncalcified matrix in Phospho1 KO mice wasattenuated compared with surrounding normally mineralised bone. The extent and position of this aberrantbiomineralisation varied considerably between animals, contralateral limbs and anatomical sites. The mostfrequent manifestation lay, however, in the nearly complete failure of mineralisation in the bone surrounding thenumerous transverse blood vessel canals in the cortices. In conclusion, SEM disclosed defective mineralising frontsand extensive patchy osteomalacia, which has previously not been recognised. These data further confirm the roleof this phosphatase in physiological skeletal mineralisation.
