Association between cognitive social capital and all-cause mortality in Great East Japan Earthquake survivors: a prospective cohort study.

OBJECTIVES: Cognitive social capital (SC), such as attitude, trust, or norms, may help improve resilience among survivors, thus improving their health. However, the association between cognitive SC and the risk of all-cause mortality among survivors after the natural disaster has never been investigated. The purpose of the present study is to investigate the association between cognitive SC and the risk of all-cause mortality among survivors of the Great East Japan Earthquake (GEJE). STUDY DESIGN: Prospective cohort study. METHODS: We conducted a health survey on 1654 residents aged ≥18 years who lived in two areas affected by the GEJE. One year after the GEJE, between June and August 2012, cognitive SC (helping each other, trust, greeting, and solving problems together) was assessed using a self-administrated questionnaire. We divided the subjects into two groups based on response to questionnaire: "high" or "low." We obtained information on death and emigration from the Residential Registration Record and followed up on the participants from June 2012 to November 2020. The Cox proportional hazards regression analysis was used for estimating the multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of all-cause mortality according to each cognitive SC indicator. RESULTS: During the 8.5 years of follow-up, 213 subjects died (12.9%). For greeting, compared with subjects who were "high," subjects who were "low" were significantly associated with the risk of all-cause mortality (HR: 2.92, 95% CI: 1.19-7.17). No statistically significant association was observed for helping each other, trust, and solving problems together. CONCLUSION: Our findings suggest that perception of greeting may be associated with the risk of all-cause mortality in survivors after natural disasters.

Applicability of DPI formulations for novel neurokinin receptor antagonist.

A novel triple neurokinin receptor antagonist (TNRA) could have pharmaceutical efficacy for asthma and/or chronic obstructive pulmonary disease. TNRA is potentially developed as inhalation medicine. The aim of this investigation was to evaluate the applicability of dry powder inhaler (DPI) formulation for TNRA. DPI formulation containing lactose was used for this feasibility study. Mechanofusion process for surface modification was applied on lactose particles to prepare four different DPI formulations. The mixture of TNRA and lactose was administered to rats intratracheally using an insufflator. The deposition pattern and blood concentration profile of TNRA were evaluated. Although there was no significant difference in deposition on deep lungs between the four formulations, DPI formulations containing mechanofusion-processed lactose showed longer T(max) and t(1/2) and higher AUC(0-infinity) and MRT compared to that containing intact lactose. On the other hand, the contact angle measurement showed that the mechanofusion process decreased the polar part of the surface energy of the lactose. Therefore, the prolongation of the wetting of the formulated powder mixture seemed to delay the dissolution of TNRA deposited in respiratory tract. It was concluded that DPI formulation containing mechanofusion-processed lactose could be suitable for inhalation of TNRA.

Origins and insertions of the triangular fibrocartilage complex: a histological study.

The origins and insertions of the triangular fibrocartilage complex (TFCC) were examined histologically in serially sectioned fresh-frozen cadaver wrists. The radioulnar ligament arose vertically through Sharpey's fibres from a broad area in the ulnar fovea and more horizontally from a narrow area at the base of the ulnar styloid. The floor of the extensor carpi ulnaris sheath also originated firmly from the dorsal side of the fovea of the ulna, through an arrangement of Sharpey's fibres. Loose ulnocarpally oriented fibres, corresponding to a thickened ulnar joint capsule, arose from the hyaline-like cartilage matrix at the tip of the ulnar styloid and inserted onto the triquetrum without Sharpey's fibres. The ulnolunate and ulnotriquetral ligaments originated not from the ulna, but from the palmar side of the TFCC. The insertion of the TFCC into the sigmoid notch of the radius demonstrated a central transition from the fibrocartilaginous disc into hyaline cartilage and a firmer fibroosseous transition of the dorsal and palmar portions of the radioulnar ligament at the periphery.

Prevention of neutrophil-mediated hepatic ischemia/reperfusion injury by superoxide dismutase and catalase derivatives.

Our previous study demonstrated that the combination of mannosylated superoxide dismutase (Man-SOD) and succinylated catalase (Suc-CAT), both of which are designed to be targeted to liver nonparenchymal cells, is a promising approach to prevent the initial phase of hepatic ischemia/reperfusion injury induced by occlusion of the portal vein for 30 min followed by a 1-h reperfusion in mice. In this study, the preventive effects of these agents were examined on late-phase injury mediated by infiltrating neutrophils, a more severe condition than the initial one. Administration of Suc-CAT alone or with Man-SOD to mice undergoing hepatic ischemia/reperfusion significantly suppressed the expression of intercellular adhesion molecule-1 along the hepatic sinusoid and prevented neutrophil infiltration in the liver. Man-SOD and Suc-CAT also prevented the increase in plasma glutamic pyruvic transaminase and glutamic oxaloacetic transaminase activities after reperfusion lasting 3 and 6 h. Histological evaluation of liver tissues confirmed the efficacy of this treatment, suggesting that these SOD and catalase derivatives have the ability to suppress neutrophil-induced hepatic injury. These results demonstrate that targeted delivery of antioxidant enzymes to liver nonparenchymal cells is a promising approach to reducing the reactive oxygen species produced by Kupffer cells and neutrophils infiltrating into the tissue. Since Suc-CAT is partially taken up by hepatocytes via a catalase-specific uptake mechanism, such a fraction could also be involved in its preventive effect against the injury.

[The usefulness of intra-operative angiography during off-pump CABG].

BACKGROUND: Recently OPCAB has become more and more common in CABG, although one problem of OPCAB like the quality of anastomosis has not been solved yet. We discussed the usefulness of intra-operative angiography during OPCAB. METHODS: During March 1997-July 2000, 55 patients underwent OPCAB (including 35 MIDCAB cases) in our institute. Graft flow and anastomosis were examined by intra-operative or immediate post-operative angiography. RESULTS: Immediate postoperative angiography was performed in 22 MIDCAB cases. In 15 cases an excellent graft flow without stenosis could be confirmed, in 7 cases the native LAD was so small, which caused a poor flow of the LITA and three cases needed additional PTCA because of anastomosis stenosis. Intra-operative angiography was done in 9 MIDCAB and 17 OPCAB. As a result, re-anastomosis was performed in one case of MIDCAB because of severe anastomosis stenosis, one case of OPCAB had confirmed poor flow because of a small LAD, but in 24 cases an excellent graft flow could be seen on time. In 2 cases OPCAB was combined with PTCA to achieve complete revascularization. CONCLUSIONS: Intra-operative angiography is a useful strategy to confirm the surgical results quickly in OPCAB (included MIDCAB). Using such a strategy, combination of OPCAB and PTCA as a new approach for complete revascularization can be performed safe and smooth.

Histological anatomy of the triangular fibrocartilage complex of the human wrist.

The triangular fibrocartilage complex (TFCC) was studied in serial histological sections of the human wrist to reveal its three-dimensional fine structure. The TFCC consisted of a fibrocartilaginous disc proper and other fibrous components. Three-dimensionally, the distal portion of the TFCC had a hammock-like contour that partially surrounded the carpus; while the proximal ligamentous portion corresponding to the radioulnar ligament connected the radius to the ulna. The radioulnar ligament originated at the ulna from both the fovea and the basistyloid. The fibres first gathered and then bifurcated palmarly and dorsally, enclosing and partially coalescing with the proximal side of the disc before inserting around the distal rim of the sigmoid notch of the radius. The meniscus homologue, which corresponded to the ulnar internal wall of the wrist joint, was derived from a loose synovial fold adapting to the stresses from radioulnar deviation. The distal side of the disc consisted of a dense population of chondrocytes in a collagen matrix, while the proximal side was rather rich in fibres directed radioulnarly. Inside the TFCC were loose connective tissues. The histological arrangement of the TFCC is compatible with its function of supporting the carpus, stabilizing the joints and allowing smooth motion of the wrist.

Normal kinematics of the interosseous membrane during forearm pronation-supination--a three-dimensional MRI study.

We studied in vivo dynamic shape changes of the interosseous membrane (IOM) during forearm rotation using three-dimensional magnetic resonance imaging (3D-MRI), and simultaneously analysed 3D-motion of the forearm rotation. Wavy deformities were seen in the IOM in the pronated position, and similar small changes were also seen at maximum supination (average 82 degrees ) and in the neutral position. These dynamic changes mainly occurred in the membranous part of the IOM, whereas the tendinous part demonstrated minimal dynamic changes during rotation in all subjects. On the dorsal aspect, deformity around the dorsal oblique cord was seen at maximum pronation. From this 3D-MRI observation, the tendinous part is considered to be taut during rotation to provide stability between the radius and ulna, because of its straightness and less dynamic changes. The more deformable membranous part is important to allow for smooth rotation, since it lies at a distance from the rotation axis. Inelasticity developing in the membranous part from trauma may pre-dispose to pronation-supination contracture. The radius rotated around the ulna from maximum supination to 45 degrees pronation. At maximum pronation (average 75 degrees ), the radius translated average 1.8 mm palmarly and rotated average 4.0 degrees ulnarward on the ulna. Incongruity of the distal radioulnar joint, contraction of the pronator quadratus and torsion between the radius and ulna at maximum pronation may produce this irregular motion of the radius and cause the dynamic changes of the IOM.

[A case of neurocysticercosis presenting as focal seizure].

In Japan neurocysticercosis is a rare disease. We report a case of neurocysticercosis with a review of the literature. A 29-year-old man presented focal seizure on the left side. Physical and neurological findings on admission were unremarkable. CT and MRI showed a mass with ring-like enhancement and perifocal edema in the right frontal lobe, as well as multiple small masses with calcification. The main mass measuring 8 mm in diameter, was suspected as the eliptogenic focus, and was totally removed via the transcortical approach. Postsurgically seizures did not recur, and histological examination of the mass confirmed a cysticercus. A therapeutic course of albendazole and praziquantel administered postsurgically was effective for the multiple intraparenchymal masses.

Direct stimulation of osteoclastic bone resorption by bone morphogenetic protein (BMP)-2 and expression of BMP receptors in mature osteoclasts.

Bone morphogenetic proteins (BMPs) play an important role in various kinds of pattern formation and organogenesis during vertebrate development. In the skeleton, BMPs induce the differentiation of cells of chondrocytic and osteoblastic cell lineage and enhance their function. However, the action of BMPs on osteoclastic bone resorption, a process essential for pathophysiological bone development and regeneration, is still controversial. In this study, we examine the direct effect of BMPs on osteoclastic bone-resorbing activity in a culture of highly purified rabbit mature osteoclasts. BMP-2 caused a dose- and time-dependent increase in bone resorption pits excavated by the isolated osteoclasts. BMP-4 also stimulated osteoclastic bone resorption. The increase in osteoclastic bone resorption induced by BMP-2 was abolished by the simultaneous addition of follistatin, a BMP/activin binding protein that negates their biological activity. Just as it increased bone resorption, BMP-2 also elevated the messenger RNA expressions of cathepsin K and carbonic anhydrase II, which are key enzymes for the degradation of organic and inorganic bone matrices, respectively. Type IA and II BMP receptors (BMPRs), and their downstream signal transduction molecules, Smad1 and Smad5, were expressed in isolated osteoclasts as well as in osteoblastic cells, whereas type IB BMPR was undetectable. BMPs directly stimulate mature osteoclast function probably mediated by BMPR-IA and BMPR-II and their downstream molecules expressed in osteoclasts. The results presented here expand our understanding of the multifunctional roles of BMPs in bone development.

Ultrastructural study on calcification of cartilage: comparing ICR and twy mice.

Twy mice are autosomal recessive mutant mice that develop multiple progressive abnormal calcification, mainly of the cartilage or tendons of the spine and limbs. They finally succumb to severe deformation and ankylosis. We carried out an ultrastructural study on the growth plate as well as the articular and spinal disc cartilage of twy mice and control ICR mice. Knee and spinal specimens were obtained from the animals, then prepared using standard procedures. Ultrastructural observations were made on uranyl lead-stained sections and elemental analysis was carried out on unstained sections. In both twy and ICR mice, linked granules (chain granules) were observed at the pericellular matrix, but there was no remarkable difference between their presence in the growth cartilage. In the twy mice, however, chain granules were observed in the pericellular matrix, cytoplasm, and nucleus of the articular and spinal disc cartilage. These chain granules disappeared after decalcification. Elemental analyses revealed significant amounts of calcium and phosphorus in these granules. It may be significant for abnormal calcification that such chain granules were observed in the articular and spinal disc cartilage of twy mice.

In vivo motion analysis of forearm rotation utilizing magnetic resonance imaging.

OBJECTIVE: To analyse in vivo normal forearm rotation utilizing the image processing method on axial magnetic resonance imaging. DESIGN: Rotatory motion and translation of the radius and rotation of the ulna were analysed in vivo, utilizing features of the bone image; axial centre of gravity and axis of the bone. METHODS: Axial magnetic resonance images at the proximal, middle and distal portion of the right forearms of 20 healthy volunteers were examined in five rotational positions, maximum pronation, 45 degrees pronation, neutral, 45 degrees supination and maximum supination. The axis of forearm rotation, the rotation angle of the radius, the rotation of the radius around its axial centre of gravity, and the rotation of the ulna around its axial centre of gravity were calculated on these axial MR images. RESULTS: The radius rotates in a near-circular ellipse around its rotational centre located on a line through the radial head and the ulnar head from maximum supination to 45 degrees pronation. There was discrepancy between the calculated maximum rotational angle of the radius and the pronation-supination angle showed on the goniometer. This discrepancy was due to motion at the radiocarpal, midcarpal and carpometacarpal joints. The rotation of the ulna ranges within 6 degrees. At maximum pronation, there was palmar translation of the radius. CONCLUSIONS: The forearm rotation is not a simple rotatory motion but a complex motion with rotation and translation. The palmar translation of the radius at maximum pronation may be caused by incongruity of the distal radioulnar joint and contraction of the pronator quadratus muscle. RELEVANCE: To date there exist few methods for the accurate and non-invasive assessment for motion analysis of the forearm rotation. Such a technique utilizing magnetic resonance image characteristics is, however, helpful to reveal accurate self- and relative-rotatory motion of both radius and ulna as well as the translation movement on forearm rotation in normal forearm.

Structure-activity relationship of HIV-1 protease inhibitors containing alpha-hydroxy-beta-amino acids. Detailed study of P1 site.

The structure-activity relationship of HIV-1 protease (HIV-1 PR) inhibitors containing alpha-hydroxy-beta-amino acids is discussed. We demonstrated that substituent groups on the P1 aromatic rings of the inhibitors exert significant influence on their biological activity. Inhibitors bearing an alkyl or a fluorine atom at the meta and para position on their P1 benzene ring were found to be good inhibitors. We also discovered that the substitution positions of the P2 benzamides were crucial for good antiviral potency. In this study, inhibitor 48 was the most potent [IC90 (CEM/HIV-1 IIIB) 27 nM] and showed good pharmacokinetics in rats.

Dynamic changes in the shape of the triangular fibrocartilage complex during rotation demonstrated with high resolution magnetic resonance imaging.

We studied in vivo dynamic changes in the triangular fibrocartilage complex (TFCC) in ten healthy volunteers using high-resolution magnetic resonance imaging (MRI). A custom made surface coil, which was specially designed to allow movements of the wrist in all directions, was used in this study. MR images in the axial and coronal planes were acquired at maximum pronation, in the neutral position and at maximum supination. During pronation and supination, little deformity of the disc proper was seen on axial sections. In contrast, the ulnar side of the TFCC around the ulnar styloid process showed obvious dynamic changes. The ulnar head translated palmarly to the radius in supination and dorsally in pronation, while there was little change in the position of the fovea of the ulna in relation to the radius. Considering the three-dimensional structure of the TFCC, these findings suggest that the disc proper is strong enough to support the ulnar carpus with little deformity during rotation and that the triangular ligament twists at its origin. During rotation there is friction between the proximal side of the disc proper and the ulnar head. On coronal sections, the disc proper became thinner in pronation due to increased ulnar variance.

In vivo MR studies of dynamic changes in the interosseous membrane of the forearm during rotation.

In vivo dynamic changes in the interosseous membrane (IOM) during forearm rotation were studied using magnetic resonance imaging (MRI). The right forearms of 20 healthy volunteers were examined in five different rotational positions. Axial slices were obtained at the proximal quarter, the middle and the distal quarter of the forearm. The changes in shape of the IOM during rotation were observed in an axial MR plane. For each image, we measured the interosseous distance and the length of the interosseous membrane. Images of the tendinous and membranous parts of the IOM could be differentiated by thickness. There were minimal dynamic changes in the tendinous part on the MRI while the membranous part showed numerous changes during rotation. The interosseous distance and the length of the interosseous membrane were maximum from a neutral to a slightly supinated position. The tendinous part is considered to be taut during rotation to provide stability between the radius and the ulna, but the membranous part which is soft, thin and elastic, allows smooth rotation.

Hepatocyte-specific distribution of catalase and its inhibitory effect on hepatic ischemia/reperfusion injury in mice.

To explore the possibility of using catalase for the treatment of reactive oxygen species (ROS)-mediated injuries, the pharmacokinetics of bovine liver catalase (CAT) labeled with 111In was investigated in mice. At a dose of 0.1 mg/kg, more than 70% of 111In-CAT was recovered in the liver within 10 min after intravenous injection. In addition, 111In-CAT was predominantly recovered from the parenchymal cells (PC) in the liver. Increasing the dose retarded the hepatic uptake of 111In-CAT, suggesting saturation of the uptake process. This cell-specific uptake could not be inhibited by coadministration of various compounds which are known to be taken up by liver PC, indicating that the uptake mechanism of CAT by PC is very specific to this compound. The preventive effect of CAT on a hepatic ischemia/reperfusion injury was examined in mice by measuring the GOT and GPT levels in plasma. A bolus injection of CAT at 5 min prior to the reperfusion attenuated the increase in the levels of these indicators in a dose-dependent manner. These results suggest that catalase can be used for various hepatic injuries caused by ROS.

Fat suppression magnetic resonance imaging of the triangular fibrocartilage complex. Comparison with spin echo, gradient echo pulse sequences and histology.

Magnetic resonance imaging (MRI) of the triangular fibrocartilage complex (TFCC) of the wrist was performed in ten healthy volunteers using spin echo T1-weighted (SE-T1), fast spin echo T2-weighted (FSE-T2), gradient echo T2-weighted (GRE-T2) and fat suppression spin echo T1-weighted (FS-T1) images. The images were obtained in the coronal plane and were compared to the corresponding histological coronal sections obtained from five fresh frozen cadavers. In our analysis, the FS-T1 pulse sequence visualized the details of the TFCC best, followed by the GRE-T2 images. Delineation of the TFCC on the SE-T1 and the FSE-T2 was poor. The coronal morphology of the TFCC represented on the fat suppression image was almost identical to the corresponding histological sections. We conclude that the fat suppression MRI clearly shows the complex structure of the TFCC and is useful for the morphological evaluation of the TFCC.

Three-dimensional magnetic resonance imaging of the interosseous membrane of forearm: a new method using fuzzy reasoning.

We now report newly developed three-dimensional magnetic resonance imaging (3D-MRI) system which is based on semiautomatic tissue extraction from the axial MR images utilizing the fuzzy reasoning calculation method and 3D-image reconstruction with surface rendering. We also studied normal in vivo dynamic changes of the interosseous membrane (IOM) of forearm during rotation using this 3D-MRI. Serial axial MRI of right forearms of five healthy volunteers was obtained in five rotational positions, and extraction and 3D-reconstruction of the radius, ulna, and IOM was made using the system. Extraction results were well with the fuzzy reasoning method. 3D-MRI of the radius and ulna, IOM were reconstructed from these images respectively, and their 3D-shapes were almost identical to the anatomic shape. 3D-MRI showed there were wavy deformities on the IOM in pronation position in the all five subjects and dorsiflexion on the most dorsal portion of the IOM at maximum supination in three forearms. In neutral position, the IOM of all five volunteers was almost flat. From anatomic orientation, these dynamic changes of the IOM mainly occurred at the membranous portion, which is soft, thin, and elastic. Otherwise, the tendinous portion which is a thick and strong complex of 5 to 10 bundles run from proximal one third of the radius to distal one fourth of the ulna, demonstrated minimal dynamic changes on the 3D-MRI. Therefore, the tendinous portion is considered to be taut during rotation to provide stability between the radius and the ulna, while the membranous portion is easy to deform and allowing smooth rotation. Furthermore, because of wide-use, our 3D-MRI system is useful for in vivo analysis of soft tissue kinesiology in normal and abnormal musculoskeletal systems.

Targeted delivery and improved therapeutic potential of catalase by chemical modification: combination with superoxide dismutase derivatives.

Four types of bovine liver catalase (CAT) derivatives, succinylated (Suc-CAT), galactosylated (Gal-CAT), mannosylated (Man-CAT), and polyethylene glycol conjugate (PEG-CAT), were synthesized and their pharmacokinetics and therapeutic potential in a hepatic ischemia/reperfusion injury model were studied in mice. About 90% of the CAT enzymatic activity was retained after chemical modification. Biodistribution studies showed that 111indium (111In)-Gal-CAT accumulated selectively in the liver parenchymal cells as 111In-CAT, whereas an increased amount of 111In-Suc-CAT and 111In-Man-CAT was delivered to liver nonparenchymal cells. 111In-PEG-CAT exhibited prolonged retention in plasma. Pharmacokinetic analysis revealed that the hepatic uptake clearances of 111In-Suc-CAT, 111In-Gal-CAT, and 111In-Man-CAT were much greater than that of 111In-CAT, whereas that of 111In-PEG-CAT was very small. In the ischemia/reperfusion injury model, in which hepatic injury was induced by occlusion of the portal vein for 30 min followed by 1 h reperfusion, the elevation of plasma glutamic pyruvic transaminase and glutamic oxaloacetic transaminase levels was slightly inhibited by treatment with native CAT or Gal-CAT. PEG-CAT was less potent. In contrast, Suc-CAT and Man-CAT effectively suppressed the increase in plasma glutamic pyruvic transaminase and glutamic oxaloacetic transaminase. Coinjection of mannosylated superoxide dismutase marginally improved the inhibitory effects of CAT derivatives. These results demonstrate that targeted CAT delivery to liver nonparenchymal cells via chemical modification is a promising approach to prevent hepatic injuries caused by reactive oxygen species. The potential usefulness of combining of CAT and superoxide dismutase derivatives is also demonstrated.

The effects of tensile load on the metabolism of cultured chondrocytes.

The effect of cyclic tensile load on articular cartilage metabolism was investigated experimentally using 12 Japanese White rabbits. Chondrocytes obtained from the knee joints were cultured on plates with flexible silicone rubber bases. They were subjected to a cyclic (3 seconds on and 3 seconds off) tensile load for 24 hours with a maximum increase in area of 17%. Proteoglycan synthesis, collagen synthesis, and tissue inhibitors of metalloproteinases production by the chondrocytes under the load were quantified and compared with those produced by the control cells in an unloaded condition. The cultured chondrocytes under the cyclic tensile load perpendicularly aligned to the direction of the tensile load. Collagen synthesis and tissue inhibitors of metalloproteinases production increased significantly under the cyclic tensile load, although no significant change in proteoglycan synthesis was observed. These results suggested that the cyclic tensile load on the chondrocytes contribute to the regulation of articular cartilage metabolism in part.

Human osteoclast-like cells are formed from peripheral blood mononuclear cells in a coculture with SaOS-2 cells transfected with the parathyroid hormone (PTH)/PTH-related protein receptor gene.

Subclones of the human osteosarcoma cell line SaOS-2 were established by transfecting with an expression vector containing the human PTH/PTH-related protein (PTHrP) receptor, and their abilities to support osteoclast-like multinucleated cell (OCL) formation were examined in coculture with mouse or human hemopoietic cells. Of four subclones examined, SaOS-2/4 and SaOS-4/3 bound high levels of [125I]-PTH and produced a significant amount of cAMP in response to PTH. OCLs were formed in response to PTH in the cocultures of mouse bone marrow cells with either SaOS-2/4 cells or SaOS-4/3 cells. Human OCLs were also formed in response to PTH in the coculture of SaOS-4/3 cells and human peripheral blood mononuclear cells. Adding dexamethasone together with PTH greatly enhanced PTH-induced human OCL formation. Like mouse OCLs, human OCLs formed in response to PTH were tartrate-resistant acid phosphatase positive, expressed abundant calcitonin receptors and vitronectin receptors, and formed resorption pits on dentine slices. Other osteotropic factors such as 1alpha,25-dihydroxyvitamin D3, prostaglandin E2, and interleukin 6 plus soluble interleukin 6 receptors failed to induce mouse and human OCLs in cocultures with SaOS-4/3 cells. Both mouse and human OCL formation supported by SaOS-4/3 cells were inhibited by either adding an antibody against macrophage-colony stimulating factor or adding granulocyte/macrophage-colony stimulating factor. Thus, it is likely that human and mouse OCL formation supported by SaOS-4/3 cells are similarly regulated. These results indicate that the target cells of PTH for inducing osteoclast formation are osteoblast/stromal cells but not osteoclast progenitor cells in the coculture. This coculture model will be useful for investigating the abnormalities ofosteoclast differentiation and function in human metabolic bone diseases.