PHOSPHO1 is essential for mechanically competent mineralization and the avoidance of spontaneous fractures

Huesa, C., Yadav, M., Finnila, M.A.J., Goodyear, S.R., Robins, S.P., Tanner, K.R. , Aspden, R.M., Millán, J.L. and Farquharson, C. (2011) PHOSPHO1 is essential for mechanically competent mineralization and the avoidance of spontaneous fractures. Bone, 48(5), pp. 1066-1074. (doi: 10.1016/j.bone.2011.01.010)

Abstract

Phosphatases are essential for the mineralization of the extracellular matrix within the skeleton. Their precise identities and functions however remain unclear. PHOSPHO1 is a phosphoethanolamine/phosphocholine phosphatase involved in the generation of inorganic phosphate for bone mineralization. It is highly expressed at sites of mineralization in bone and cartilage. The bones of Phospho1^-/- mice are hypomineralized, bowed and present with spontaneous greenstick fractures at birth. In this study we show that PHOSPHO1 is essential for mechanically competent mineralization that is able to withstand habitual load. Long bones from Phospho1^-/- mice did not fracture during 3- point bending but deformed plastically. With dynamic loading nanoindentation the elastic modulus and hardness of Phospho1^-/- tibia were significantly lower than wild-type tibia. Raman microscopy revealed significantly lower mineral:matrix ratios and lower CO32- substitutions in Phospho1^-/- tibia. The altered dihydroxylysinonorleucine/hydroxyllysinonorleucine and pyridoline/deoxypyridinoline collagen crosslink ratios indicated possible changes in lysyl hydroxylase- 1 activity and/or bone mineralization status. The bone formation and resorption markers, N-terminal propeptide and C-terminal telopeptide of Type I collagen, were both increased in Phospho1^-/- mice and this we associated with increased bone modelling during fracture repair or an attempt to model a mechanically competent bone capable of withstanding physiological load. In summary these data indicate that Phospho1^-/- bones are hypomineralized and, consequently, are softer and more flexible. An inability to withstand physiological loading may explain the deformations noted. We hypothesize that this phenotype is due to the reduced availability of inorganic phosphate to form hydroxyapatite during mineralization, creating an under-mineralized yet active bone.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Tanner, Professor Kathleen
• Authors: Huesa, C., Yadav, M., Finnila, M.A.J., Goodyear, S.R., Robins, S.P., Tanner, K.R., Aspden, R.M., Millán, J.L., and Farquharson, C.
• College/School: College of Science and Engineering > School of Engineering > Biomedical Engineering; College of Science and Engineering > School of Physics and Astronomy
• Journal Name: Bone
• Publisher: Elsevier Inc.
• ISSN: 8756-3282
• Published Online: 25 January 2011