Chemokines are characterized by the homing activity of leukocytes to targeted inflammation sites. Recent research indicates that chemokines play more divergent roles in various phases of pathogenesis as well as immune reactions. The chemokine receptor, CCR1, and its ligands are thought to be involved in inflammatory bone destruction, but their physiological roles in the bone metabolism in vivo have not yet been elucidated. In the present study, we investigated the roles of CCR1 in bone metabolism using CCR1-deficient mice. Chemokines are initially identified as small cytokines that direct the homing of circulating leukocytes into sites of inflammation (1). Chemokines are now recognized to be major factors in inflammation and immune development as well as tumor growth, angiogenesis, and osteolysis. Chemokine receptors are expressed in a well organized spatiotemporal manner in various types of leukocytes, including lymphocytes, granulocytes, and macrophages. They facilitate the recruitment of these cells into inflammatory sites during the appropriate phase of inflammation.Recent findings indicate that chemokine receptors, including CCR1 7 and its related chemokines, CCL3 and CCL9, are involved in the pathogenesis of a variety of diseases. In particular, CCL3 (also called MIP-1␣), a major pro-inflammatory chemokine produced at inflammatory sites, appears to play a crucial role in pathological osteoclastogenesis (2, 3). In osteolytic bone inflammation (e.g. rheumatoid arthritis-associated bone destruction), CCL3 induces ectopic osteoclastogenesis (4) * This work was supported in part by Grant H19-nano-012 from the Ministry of Health, Labor and Welfare (to K. Y.) and by a research fellowship from the Japan Society for the Promotion of Science for Young Scientists (2007Scientists ( -2009 ( The abbreviations used are: CCR, C-C chemokine receptor; M-CSF, macrophage-colony stimulation factor; BALP, bone-specific alkaline phosphatase; CCL, C-C chemokine ligand; MCP-1, macrophage chemoattractant protein-1; MIP-1, macrophage inflammatory protein-1; CT, computed tomography; PTX, pertussis toxin from Bordetella pertussis; RANK, receptor activator of NF-B; RANKL, receptor activator of NF-B ligand; RANTES, regulated upon activation normal T expression and secreted; TRAP, tartrate-resistant acid phosphatase; NTx, N-telopeptides.

Adhesion of yeast-form C. albicans was indifferent to surface roughness. In contrast, mycelial adhesion increased with surface roughness of the resin because mycelia infiltrated the minute protuberances on rough surfaces.

The fine structure of prostatic calculi has not been elucidated yet, although the chemical components were reported in detail. We studied the primary or endogenous calculi removed from eight human prostates by secondary scanning electron microscopy, backscattered electron imaging, energy-dispersive X-ray microanalysis and X-ray diffraction. The primary calculi containing Mg, Zn and S, besides Ca and P were basically classified into four stone groups (I-IV) by fine structure and mineral components. Stone I had the core deposits of calcospherites showing concentric rings and the laminated deposits concentrically around the core. Their deposits were identified as apatite. Stone II was occupied with the calcospherite deposits of apatite although the stone growth showed a rough concentric formation. Stone III contained the core of calcospherites and concentric laminated structures, similar to a smaller type of group I, whereas the wider peripheral region was deposited with needle-like structures, identified as calcium oxalates. Stone IV had the core deposits containing small hexahedral structures, identified as whitlockite, which were surrounded with several incompletely concentric laminated bands of apatite. Whitlockite crystals were also found between the fused large calculi. The initial and formative calculi were basically observed as the deposition of mineralizing spherical structures suggesting variously sized corpora amylaceous bodies. Thus, the primary prostatic calculi of stones I-III will begin from the mineralization of amylaceous bodies as a core, while the organic substances, which form stone IV, might be derived from the simple precipitation of prostatic secretion.

We have previously indicated that a single injection of alendronate, one of the nitrogen-containing bisphosphonates (NBPs), affects murine hematopoietic processes, such as the shift of erythropoiesis from bone marrow (BM) to spleen, disappearance of BM-resident macrophages, the increase of granulopoiesis in BM and an increase in the number of osteoclasts. NBPs induce apoptosis and the formation of giant osteoclasts in vitro and/or in patients undergoing long-term NBP treatment. Therefore, the time-kinetic effect of NBPs on osteoclasts needs to be clarified. In this study, we examined the effect of alendronate on mouse osteoclasts and osteoclastogenesis. One day after the treatment, osteoclasts lost the clear zone and ruffled borders, and the cell size decreased. After 2 days, the cytoplasm of osteoclasts became electron dense and the nuclei became pyknotic. Some of the cells had fragmented nuclei. After 4 days, osteoclasts had euchromatic nuclei attached to the bone surface. Osteoclasts had no clear zones or ruffled borders. After 7 days, osteoclasts formed giant osteoclasts via the fusion of multinuclear and mononuclear osteoclasts. These results indicate that NBPs affect osteoclasts and osteoclastogenesis via two different mechanisms.

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