Papers by Author: Jee Wook Lee

Abstract: Measurements of bone mineral density (BMD) cannot accurately predict the risk of bone fracture in some clinical cases; however, BMD is a useful index for assessing the bone condition. Recently, various parameters related to bone strength have been investigated. Among them, we have focused on the preferential orientation of biological apatite (BAp) crystallites analyzed by microbeam-X-ray diffraction, a powerful tool for analyzing BAp crystallites in bones. BAp, a dominant component of bone, is an anisotropic ionic crystal with a hexagonal lattice. In this study, we investigated the mechanism underlying BAp orientation during endochondral or membranous ossification by administering macrophage colony-stimulating factor (M-CSF) to osteopetrotic (op/op) mice lacking M-CSF. op/op mice were treated with intraperitoneal injections of 5 μg recombinant human M-CSF (rhM-CSF); the first injection was administered on the 14th day after birth. In the treated op/op mice, the bone marrow cavities expanded significantly, and this expansion was accompanied by an increase in the number of osteoclasts. Moreover, the degree of BAp orientation along the longitudinal axis was higher in the treated group than in the untreated group. These results suggest that M-CSF is one of the important parameters controlling the preferential alignment of the BAp c-axis.

Abstract: Our group focused on the preferential degree of biological apatite (BAp) c-axis, an important bone quality parameter based on the microstructural anisotropy in intact, pathological, and regenerated bones. The preferential degree of the BAp c-axis strongly depends on the bone position, in vivo stress distribution, bone growth, degree of pathology and regeneration, activity of bone cells, gene defect, etc. We attempted to challenge clarification of the BAp preferential alignment formation mechanism and control the degree of BAp orientation by using an anisotropic biomaterial design to develop suitable distribution of the BAp c-axis orientation.

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.

Abstract: Absorption and formation of hard tissues are repeated in vivo by the activity of osteoclast and osteoblast, respectively. The preferential alignment of BAp or collagen fibril is thought to be closely related to the activity of the bone cells. In this study, changes in bone mineral density (BMD) and preferential alignment of biological apatite (BAp) were examined focusing on the role of osteoblast using the model of osteopetrotic (op/op) mice in which osteoblast activity was normal but the expression of osteoclast was reduced. Osteopetrotic (op/op) mice and their normal littermates aged 5, 12 and 24 weeks were analyzed. The BMD and BAp texture of femoral diaphysis were measured using peripheral quantitative computed tomography (pQCT) and a microbeam X-ray diffractometer system with a 50 µmφ diameter beam spot respectively. The decrease in osteoclast expression induced both the reduction of the skeletal system and calcification of the medullary cavity, which are typical features of osteopetrosis. As a result, the shape, BMD and preferential BAp alignment of the femur in the op/op mice were remarkably different from those in the control group. At the center of the femoral diaphysis, BMD in the cortical area showed no significant difference between the two groups, but preferential alignment of the BAp c-axis in the op/op mice group had a lower value than that in the control group. This suggests that the decrease in the number of osteoclasts suppresses normal remodeling, resulting in a decrease in bone quality, especially the preferential alignment of the BAp c-axis.

Abstract: A dominant inorganic substance in hard tissue is known to be a biological apatite (BAp)^nano-crystal which basically crystallizes in an anisotropic hcp lattice, and the BAp c-axis is parallel to extended collagen fibrils. We applied the microbeam X-ray diffractometer system with an incident beam spot 100µm or 50µm in diameter to the original, regenerated and pathological hard tissues in order to analyze the preferential alignment of the BAp c-axis as a parameter of bone quality closely relating to the mechanical function. We conclude that the BAp orientational distribution in the hard tissues is a new measure to evaluate stress distribution in vivo, nano-scale microstructure and the related mechanical function, healing process of the regenerated bone and progress of the bone diseases.