The CC chemokine receptor 5 (CCR5) is a G protein-coupled receptor that regulates chemotaxis and effector functions of immune cells. It also serves as the major co-receptor for the entry of human immunodeficiency virus (HIV). Recently, CCR5 inhibitors have been developed and used for the treatment or prevention of HIV infections. Additionally, it has been identified that CCR5 controls bone homeostasis by regulating osteoclastogenesis and the communication between osteoblasts and osteoclasts. However, the effects of CCR5 inhibition on bone tissue in elderly patients are unknown. This study aimed to examine the bone phenotype of aged CCR5 knockout (KO) mice. Femoral and tibial bones were isolated from 12-month and 18-month old wild-type (WT) and CCR5 KO mice, and microcomputed tomography and histology analyses were performed. Twelve-month-old CCR5 KO mice exhibited a decreased trabecular bone mass and cortical bone thickness in both femoral and tibial bones compared with agematched WT mice. Eighteen-month-old mice also showed a decreased trabecular bone mass in femurs compared with control WT mice, but not in tibial bones. Unlike in 12-month-old mice, the cortical margin of femurs and tibias in 18-month-old mice were rough, likely because they were aggravated by the deficiency of CCR5. Overall, our data suggest that the deficiency of CCR5 with aging can cause severe bone loss. When CCR5 inhibitors or CCR5 inactivating technologies are used in elderly patients, a preventive strategy for bone loss should be considered.

Teeth and bones are highly mineralized tissues containing inorganic minerals such as calcium phosphate, and a growing number of evidences show that their mineral content is associated with many diseases. Although the quantification of mineral contents by micro-computed tomography(micro- CT) has been used in diagnosis and evaluation for treating bone diseases, its application for teeth diseases has not been well established. In this study, we attempted to estimate a usefulness of a high-resolution micro-CT in analysis of human teeth. The teeth were scanned by using the Skyscan 1172 micro-CT. In order to measure tooth mineral content, beam hardening effect of the machine was corrected with a radiopaque iodinecontaining substance, iodoacetamide. Under the maximum resolution of 6.6 μm, X-ray densities in teeth and hydroxyapatite standards were obtained with Hounsfield unit (HU), and they were then converted to an absolute mineral concentration by a CT Analyzer software. In enamel layer of cusp area, the mean mineral concentration was about 2.14 mg/mm3 and there was a constant mineral concentration gradient from the enamel surface to the dentinoenamel junction. In the dentin of middle 1/3 of tooth, the mean mineral concentration was approximately 1.27 mg/mm3 and there was a constant mineral concentration gradient from the outer of root to the pulp side, ranging from 1.3 to 1.06 mg/mm3. In decay region of dentin, the mineral content was gradually decreased from the intact inner side to the decayed surface. These results suggest that high-resolution micro-CT can be as a useful tool for non-invasive measurement of mineral concentration in teeth.