Papers by Keyword: Op/Op Mouse

Abstract: The preferred crystallographic orientation of the biological apatite (BAp) c-axis has been shown to be one of the important bone quality indices that sensitively reflect in vivo stress distribution and dominate bone mechanical functions. The BAp orientation is expected to be regulated by bone modeling or remodeling by osteoblasts and osteoclasts whose primary functions are bone formation and absorption, respectively. Mouse with macrophage colony-stimulating factor (M-CSF) deficiency-induced osteopetrosis (op/op mouse) is a suitable animal model to elucidate the role of osteoclasts in the development of BAp orientation. In this study, the mandibles of 5-week-old mice were used because their mandible is subjected to complicated stresses including a biting stress locally applied just around the roots of the teeth and a bending stress applied along the mesiodistal axis of the mandibular body, and the response to the stress distribution is important to the formation of BAp orientation. The normal mouse mandible (control) has a one-dimension preferred BAp orientation in the mesiodistal direction, but just near the tooth root, the direction of BAp orientation changes locally to that of the tooth root responding to a biting stress. In the op/op mouse, the preferred BAp orientation only along the mesiodistal direction is found, but the degree is quite lower than that in normal mice. Moreover, the effect of biting was not observed in op/op mice because these mice are devoid of teeth eruption and are unable to bite. This suggests that M-CSF plays a critical role in forming the optimal BAp orientation, and therefore, the op/op mouse without osteoclasts cannot fully develop the appropriate bone microstructure in response to in vivo stress distribution, although BAp orientation is very sensitive to local in vivo stresses in normal animals with normal osteoclast function.

Abstract: The diagnosis of hard tissues is generally carried out by bone mineral density (BMD) measurement as a bone quantity parameter. BMD, however, does not necessarily explain bone fracture risks in some clinical cases. Recently, various parameters relating to bone strength have been investigated. These additional parameters, so-called bone quality, reflect intrinsic bone conditions. We have been studying the preferential alignment of the biological apatite (BAp) c-axis among various bone quality parameters. BAp, a dominant component of hard tissue, is an ionic crystal that crystallizes in a hexagonal lattice accompanied with the anisotropic property. In this article, we investigated the osteoclast role in the recovery process of BAp orientation during bone regeneration using osteopetrotic (op/op) mice in which the number of osteoclasts decreases. A surgically drilled, 500-μm diameter hole on each tibia of both control and op/op 8-week-old mice was introduced from the medial surface into the medullary cavity located at a 30% length from the proximal tibia end. After surgery, tibiae injuries were regularly observed by in situ micro-CT, and then the mice were sacrificed four to eight weeks after surgery. BAp orientation was analyzed in and near the regenerated portion by the microbeam X-ray diffraction system. As a result, we found the insufficient recovery of BAp orientation in spite of the apparent repair of bone appearance and quantity from CT images, even eight weeks after surgery in both cases of control and op/op mice. We conclude that this defective animal model can be used to evaluate bone quantity and quality at the cortical portion during bone regeneration in gene-defect mice in which the expression of bone cells is controlled, for example.

Abstract: Bone microstructure and its functions are maintained by the activity of bone cells such as osteoclast for bone resorption and osteoblast for bone formation. In this study, we examined the role of osteoclast on the formation of the preferential orientation of biological apatite (BAp) as a bone quality parameter using OPG-KO and op/op mouse models in which the expression of osteoclast increases for osteoporosis and decreases for osteopetrosis. The orientation degree of the BAp c-axis was analyzed by a microbeam X-ray diffraction system. We found more decrease in the preferential alignment of the BAp c-axis along the longitudinal direction of bone in the femoral bones of both OPG-KO and op/op mice at 12 weeks compared with normal control mice. We concluded that changes in the amount and activity of osteoclast affect BAp alignment, resulting in the degradation of bone microstructure in osteoporosis and osteopetrosis.