PHOSPHO1 is Essential for Normal Bone Fracture Healing

Introduction: Bone fracture healing is regulated by a series of complex physicochemical and biochemical processes. One of these processes is bone mineralization, which is vital for normal bone development. Phosphatase, orphan 1 (PHOSPHO1), a skeletal tissue-specific phosphatase, has been shown to be involved in the mineralization of the extracellular matrix and to maintain the structural integrity of bone. In this study, we examined how PHOSPHO1-deficiency might affect the healing and quality of the fractured bones in mice.
Methods: Rodded immobilized fracture surgery on the right tibia of control wild type (WT) and Phospho1-/- mice (n=16 for each group; mixed gender each group carrying equal number of males and females) at eight weeks of age. Bone was left to heal for four weeks and then the mice were euthanized and their tibias were analyzed using X-ray, Micro-Computed Tomography (μCT), histology, histomorphometry and three-point bending tests.
Results: The μCT and X-ray analyses revealed a significant increase of bone surface over bone volume (BS/BV), bone surface over tissue volume (BS/TV) and trabecular number and decrease in trabecular thickness and separation in Phospho1-/-callus in comparison to the WT callus. These observations were confirmed by histomorphometry. There was a marked increase of osteoid volume over bone volume (OV/BV) in the Phospho1-/- callus. The three-point bending test showed that Phospho1-/- fractured bone had more of an elastic characteristic than the WT bone.
Conclusion: Our work suggests that PHOSPHO1 plays an integral role during bone fracture repair and may be a therapeutic target to improve the fracture healing process.
Keywords: Bone mineralization, PHOSPHO1, endochondral ossification, bone fracture repair, Phospho1-/- mice.