Serum periostin levels correlate with severity of intervertebral disc degeneration.

PURPOSE: Periostin, an extracellular matrix protein closely related to mechanical stress, inflammation, and ageing, has been implicated in intervertebral disc degeneration (IVDD) in basic research. However, it has not been examined in clinical cases. This study aimed to evaluate the association between IVDD severity and serum periostin concentration as well as to analyse potential associations between IVDD and clinical and demographic factors. METHODS: This retrospective cohort study included 198 patients who underwent lumbar disc herniation and lumbar canal stenosis between January 2020 and December 2022. The severity of IVDD was evaluated using the Pfirrmann grading, whereas serum periostin levels were measured using ELISA kits. Clinical demographics, including age, sex, body mass index, comorbidities, psoas muscle index, and spinal disease, were also recorded. RESULTS: This study demonstrated a significant correlation between high serum periostin levels and IVDD severity, as indicated by a high cumulative Pfirrmann score. Serum periostin levels were identified as an independent risk factor for IVDD in a multivariate regression model. Correlation analysis showed a correlation between periostin levels and Pfirrmann grade at each lumbar level (ρ = 0.458-0.550, p < 0.001) and a strong correlation with cumulative Pfirrmann score (ρ = 0.690, p < 0.001). CONCLUSION: The higher the serum periostin level, the higher the cumulative Pfirrmann score. Multivariate analysis showed that serum periostin was an independent risk factor for IVDD. Periostin levels may be a clinically suitable and useful biomarker for diagnosing IVDD, estimating disease progression and activity, providing prognostic information, and evaluating treatment options.

Nupr1 deficiency downregulates HtrA1, enhances SMAD1 signaling, and suppresses age-related bone loss in male mice.

Nuclear protein 1 (NUPR1) is a stress-induced protein activated by various stresses, such as inflammation and oxidative stress. We previously reported that Nupr1 deficiency increased bone volume by enhancing bone formation in 11-week-old mice. Analysis of differentially expressed genes between wild-type (WT) and Nupr1-knockout (Nupr1-KO) osteocytes revealed that high temperature requirement A 1 (HTRA1), a serine protease implicated in osteogenesis and transforming growth factor-ß signaling was markedly downregulated in Nupr1-KO osteocytes. Nupr1 deficiency also markedly reduced HtrA1 expression, but enhanced SMAD1 signaling in in vitro-cultured primary osteoblasts. In contrast, Nupr1 overexpression enhanced HtrA1 expression in osteoblasts, suggesting that Nupr1 regulates HtrA1 expression, thereby suppressing osteoblastogenesis. Since HtrA1 is also involved in cellular senescence and age-related diseases, we analyzed aging-related bone loss in Nupr1-KO mice. Significant spine trabecular bone loss was noted in WT male and female mice during 6-19 months of age, whereas aging-related trabecular bone loss was attenuated, especially in Nupr1-KO male mice. Moreover, cellular senescence-related markers were upregulated in the osteocytes of 6-19-month-old WT male mice but markedly downregulated in the osteocytes of 19-month-old Nupr1-KO male mice. Oxidative stress-induced cellular senescence stimulated Nupr1 and HtrA1 expression in in vitro-cultured primary osteoblasts, and Nupr1 overexpression enhanced p16ink4a expression in osteoblasts. Finally, NUPR1 expression in osteocytes isolated from the bones of patients with osteoarthritis was correlated with age. Collectively, these results indicate that Nupr1 regulates HtrA1-mediated osteoblast differentiation and senescence. Our findings unveil a novel Nupr1/HtrA1 axis, which may play pivotal roles in bone formation and age-related bone loss.

How long will it take to reach the gender diversity goal for orthopaedics in Japan?

BACKGROUND: In Japan, orthopaedics is one of the medical fields with the lowest proportion of women. This study analyses the change in gender diversity over the past decade and estimates the time required to achieve the 30% gender diversity goal, according to the critical mass in Japan in 2020. METHODS: We investigated the demographic composition of orthopaedic surgeons in 2020 by age group, the gender ratio of the main clinical fields from 2010 to 2020, and estimated the time required for the bottom 10 (i.e., least diverse) medical departments in Japan to reach the proportion of 30% women. We used simple linear regression analyses to clarify the number of years. RESULTS: In 2020, the population pyramid of orthopaedic surgeons showed that those in their 50s were the largest component with 24.1%, followed by those in their 40s and 30s with 22.3% and 19.4%, respectively. The percentage of women orthopaedic surgeons increased slightly from 4.1% in 2010 to 5.7% in 2020. This means that to achieve the proportion of 30% women at the current annual increase rate, orthopaedics would require up to 160 years, cardiovascular 149 years, and neurosurgery 135 years. CONCLUSION: Contrary to the recent increase in the number of women physicians, there has been only a slight increase in the number of women orthopaedic surgeons over the past decade. Moreover, the number of young male orthopaedic surgeons has decreased. As current orthopaedic surgeons age and retire, Japan will soon face an overall shortage of orthopaedic surgeons. Issues that must still be addressed in Japanese orthopaedics include educating men and women about gender diversity and bias, changing stereotypes about surgical lifestyles, improving work-life balance, and diligent and collaborative efforts at both the individual and community levels.

Cardiopulmonary Cement Embolism Following Cement-Augmented Pedicle Screw Fixation: A Narrative Review.

Fixation using cement-augmented pedicle screws (CAPS) is being increasingly performed. However, CAPS-associated cement leakage is a critical problem that can lead to cardiopulmonary cement embolism (CPCE). This narrative review aimed to explore the incidence of and risk factors and treatment strategies for CPCE and cement leakage-related complications after CAPS fixation. Data were extracted from each article, including characteristics of CPCE after CAPS fixation (incidence, location, diagnostic method and criteria, treatment, and outcome and prognosis). Overall, 28 case series and 14 case reports that met the inclusion criteria were included. Of the 1974 cases included in the review, CPCE was noted in 123, symptomatic CPCE in 35, and death in six, respectively. The frequencies of PCE and symptomatic PCE after CAPS fixation were 6% (range: 0-28.6%) and 1.3% (range: 0-26%), respectively. The range of frequencies of PCE and symptomatic PCE after CAPS fixation may have been wide because the definition of CPCE and data collection methods differed among the reports analyzed. Since PCE due to large cement emboli may be primarily related to the surgical technique, improved technique, such as minimizing the number of CAPSs by injecting low-volume high-viscosity cement at low velocity and pressure, and careful observation of cement leakage during CAPS insertion may reduce PCE associated with cement leakage. Spinal surgeons should pay more attention to the occurrence of CPCE during and after CAPS insertion, which can cause serious complications in some patients.

A novel role of helix-loop-helix transcriptional factor Bhlhe40 in osteoclast activation.

The basic helix-loop-helix transcriptional factor, Bhlhe40 has been shown as a crucial regulator of immune response, tumorigenesis, and circadian rhythms. We identified Bhlhe40 as a possible regulator of osteoclast differentiation and function by shRNA library screening and found that Bhlhe40 was required for osteoclast activation. Bhlhe40 expression was induced in bone marrow macrophages (BMMs) by RANKL, whereas the expression of its homolog Bhlhe41 was decreased in osteoclastogenesis. µCT analysis of tibias revealed that Bhlhe40 knockout (KO) mice exhibited increased bone volume phenotype. Bone morphometric analysis showed that osteoclast number and bone resorption were decreased in Bhlhe40 KO mice, whereas significant differences in the osteoblast parameters were not seen between wild-type (WT) and Bhlhe40 KO mice. In vitro culture of BMMs showed that Bhlhe40 deficiency did not cause difference in osteoclast formation. In contrast, bone resorption activity of Bhlhe40 KO osteoclasts was markedly reduced in comparison with that of WT osteoclasts. Analysis of potential target genes of Bhlhe40 using data-mining platform ChIP-Atlas (http://chip-atlas.org) revealed that predicted target genes of Bhlhe40 were related to proton transport and intracellular vesicle acidification. We then analyzed the expression of proton pump, the vacuolar (V)-ATPases which are responsible for bone resorption. The expression of V-ATPases V1c1 and V0a3 was suppressed in Bhlhe40 KO osteoclasts. In addition, Lysosensor yellow/blue DND 160 staining demonstrated that vesicular acidification was attenuated in vesicles of Bhlhe40 KO osteoclasts. Furthermore, analysis with pH-sensitive fluorescent probe showed that proton secretion was markedly suppressed in Bhlhe40 KO osteoclasts compared to that in WT osteoclasts. Our findings suggest that Bhlhe40 plays a novel important role in the regulation of acid production in osteoclastic bone resorption.

Leukemia/lymphoma-related factor (LRF) or osteoclast zinc finger protein (OCZF) overexpression promotes osteoclast survival by increasing Bcl-xl mRNA: A novel regulatory mechanism mediated by the RNA binding protein SAM68.

RANKL induces NFATc1, a key transcriptional factor to induce osteoclast-specific genes such as cathepsin K, whereas transcriptional control of osteoclast survival is not fully understood. Leukemia/lymphoma-related factor (LRF) in mouse and osteoclast zinc finger protein (OCZF) in rat are zinc finger and BTB domain-containing protein (zBTB) family of transcriptional regulators, and are critical regulators of hematopoiesis. We have previously shown that differentiation and survival were enhanced in osteoclasts from OCZF-Transgenic (Tg) mice. In the present study, we show a possible mechanism of osteoclast survival regulated by LRF/OCZF and the role of OCZF overexpression in pathological bone loss. In the in vitro cultures, LRF was highly colocalized with NFATc1 in cells of early stage in osteoclastogenesis, but only LRF expression persisted after differentiation into mature osteoclasts. LRF expression was further enhanced in resorbing osteoclasts formed on dentin slices. Osteoclast survival inhibitor such as alendronate, a bisphosphonate reduced LRF expression. Micro CT evaluation revealed that femurs of OCZF-Tg mice showed significantly lower bone volume compared to that of WT mice. Furthermore, OCZF overexpression markedly promoted bone loss in ovariectomy-induced osteolytic mouse model. The expression of anti-apoptotic Bcl-xl mRNA, which is formed by alternative splicing, was enhanced in the cultures in which osteoclasts are formed from OCZF-Tg mice. In contrast, the expression of pro-apoptotic Bcl-xs mRNA was lost in the culture derived from OCZF-Tg mice. We found that the expression levels of RNA binding splicing regulator, Src substrate associated in mitosis of 68 kDa (Sam68) protein were markedly decreased in OCZF-Tg mice-derived osteoclasts. In addition, shRNA-mediated knockdown of Sam68 expression increased the expression of Bcl-xl mRNA, suggesting that SAM68 regulates the expression of Bcl-xl. These results indicate that OCZF overexpression reduces protein levels of Sam68, thereby promotes osteoclast survival, and suggest that LRF/OCZF is a promising target for regulating pathological bone loss.

PMEPA1 and NEDD4 control the proton production of osteoclasts by regulating vesicular trafficking.

Osteoclast bone resorption activity is critically regulated to maintain bone homeostasis. Osteoclasts resorb bone by producing protons and acid hydrolase via lysosomal secretion, however, a detailed mechanism remains elusive. PMEPA1 is a vesicular membrane protein, which binds to the NEDD4 family member of ubiquitin ligases. We have previously reported that Pmepa1 is highly expressed in bone resorbing osteoclasts, and regulates bone resorption. Here, we investigated the mechanism of bone resorption regulated by PMEPA1. Mutant mice lacking NEDD4-binding domains of PMEPA1 displayed enhanced bone volume, and reduced bone resorption activity in comparison with those of WT mice. Analysis with pH-sensitive fluorescence probe revealed that proton secretion from osteoclasts significantly decreased in Pmepa1 mutant osteoclasts. Immunofluorescence analysis revealed that PMEPA1 was colocalized with NEDD4, V0A3, and V0D2 subunits of vacuolar ATPase, which regulate the proton production of osteoclasts. In addition, Nedd4 knockdown reduced bone resorption and proton secretion of osteoclasts. Furthermore, Pmepa1 mutation and Nedd4 knockdown altered the cytoplasmic distribution of components of V-ATPase and expression of autophagy-related proteins, suggesting that lysosomal secretion is affected. Collectively, these findings indicate that PMEPA1 controls proton secretion from osteoclasts via NEDD4 by regulating vesicular trafficking, and NEDD4 is an important regulator of bone resorption.

Ageing attenuates bone healing by mesenchymal stem cells in a microribbon hydrogel with a murine long bone critical-size defect model.

BACKGROUND: Despite the high incidence of fractures and pseudoarthrosis in the aged population, a potential role for the use of mesenchymal stem cells (MSCs) in the treatment of bone defects in elderly patients has not been elucidated. Inflammation and the innate immune system, including macrophages, play crucial roles in the differentiation and activation of MSCs. We have developed lentivirus-transduced interleukin 4 (IL4) over-expressing MSCs (IL4-MSCs) to polarize macrophages to an M2 phenotype to promote bone healing in an established young murine critical size bone defect model. In the current study, we explore the potential of IL4-MSCs in aged mice. METHODS: A 2 mm femoral diaphyseal bone defect was created and fixed with an external fixation device in 15- to 17-month-old male and female BALB/c mice. Microribbon (µRB) scaffolds (Sc) with or without encapsulation of MSCs were implanted in the defect sites. Accordingly, the mice were divided into three treatment groups: Sc-only, Sc + MSCs, and Sc + IL4-MSCs. Mice were euthanized six weeks after the surgery; subsequently, MicroCT (µCT), histochemical and immunohistochemical analyses were performed. RESULTS: µCT analysis revealed that bone formation was markedly enhanced in the IL4-MSC group. Compared with the Sc-only, the amount of new bone increased in the Sc + MSCs and Sc + IL4-MSC groups. However, no bridging of bone was observed in all groups. H&E staining showed fibrous tissue within the defect in all groups. Alkaline phosphatase (ALP) staining was increased in the Sc + IL4-MSC group. The Sc + IL4-MSCs group showed a decrease in the number of M1 macrophages and an increase in the number of M2 macrophages, with a significant increase in the M2/M1 ratio. DISCUSSION: IL4 promotes macrophage polarization to an M2 phenotype, facilitating osteogenesis and vasculogenesis. The addition of IL4-MSCs in the µRB scaffold polarized macrophages to an M2 phenotype and increased bone formation; however, complete bone bridging was not observed in any specimens. These results suggest that IL4-MSCs are insufficient to heal a critical size bone defect in aged mice, as opposed to younger animals. Additional therapeutic strategies are needed in this challenging clinical scenario.

Fragility fracture following total hip arthroplasty.

BACKGROUND: While periprosthetic fractures following total hip arthroplasty (THA) are a well-known phenomenon for orthopedic surgeons, fragility fractures following THA are also a significant, though less studied, concern. Furthermore, patients who have undergone THA have several additional risk factors for fragility fractures, including motor weakness, bone atrophy, and limping. The aims of this study were to evaluate the incidence of fragility fractures following THA and to clarify the characteristics of these fractures. METHODS: This study included 5678 primary THA procedures in 4589 female patients. This study evaluated body morphology data, disease type leading to THA, Japanese Orthopaedic Association hip score, range of motion of the hip joint, and medical history. Distal radius and patella fractures were defined as fragility fractures. Risk factors for fragility fractures after THA were calculated by comparing the fragility fracture group with the non-fracture group. RESULTS: Fifty-three fragility fractures were confirmed in 53 patients (distal radius fracture: 32 fractures in 32 patients, patella fracture: 21 fractures in 21 patients). In the univariate analysis, the following eight risk factors for fragility fractures were significantly different between the groups: height, weight, follow-up period, developmental dysplasia of the hip, primary osteoarthritis, abduction before THA, internal rotation before THA, and external rotation before THA. Medical histories were not significantly different between the groups. There was no difference in any study factor and in the time of occurrence between the radius fractures and patella fractures analyzed as fragility fractures. CONCLUSIONS: This study revealed that there are significant preoperative factors of fragility fractures following THA. These factors will serve as useful data for THA treatment strategies, preoperative explanations, and future studies.

Development of Silver-Containing Hydroxyapatite-Coated Antimicrobial Implants for Orthopaedic and Spinal Surgery.

The prevention of surgical site infections is directly related to the minimization of surgical invasiveness, and is in line with the concept of minimally invasive spine therapy (MIST). In recent years, the incidence of postoperative infections has been increasing due to the increased use of spinal implant surgery in patients at high risk of infection, including the elderly and easily infected hosts, the limitations of poor bone marrow transfer of antibiotics, and the potential for contamination of surgical gloves and instruments. Thus, the development of antimicrobial implants in orthopedic and spinal surgery is becoming more and more popular, and implants with proven antimicrobial, safety, and osteoconductive properties (i.e., silver, iodine, antibiotics) in vitro, in vivo, and in clinical trials have become available for clinical use. We have developed silver-containing hydroxyapatite (Ag-HA)-coated implants to prevent post-operative infection, and increase bone fusion capacity, and have successfully commercialized antibacterial implants for hip prostheses and spinal interbody cages. This narrative review overviews the present status of available surface coating technologies and materials; describes how the antimicrobial, safety, and biocompatibility (osteoconductivity) of Ag-HA-coated implants have been demonstrated for commercialization; and reviews the clinical use of antimicrobial implants in orthopedic and spinal surgery, including Ag-HA-coated implants that we have developed.

Digital Transformation Will Change Medical Education and Rehabilitation in Spine Surgery.

The concept of minimally invasive spine therapy (MIST) has been proposed as a treatment strategy to reduce the need for overall patient care, including not only minimally invasive spine surgery (MISS) but also conservative treatment and rehabilitation. To maximize the effectiveness of patient care in spine surgery, the educational needs of medical students, residents, and patient rehabilitation can be enhanced by digital transformation (DX), including virtual reality (VR), augmented reality (AR), mixed reality (MR), and extended reality (XR), three-dimensional (3D) medical images and holograms; wearable sensors, high-performance video cameras, fifth-generation wireless system (5G) and wireless fidelity (Wi-Fi), artificial intelligence, and head-mounted displays (HMDs). Furthermore, to comply with the guidelines for social distancing due to the unexpected COVID-19 pandemic, the use of DX to maintain healthcare and education is becoming more innovative than ever before. In medical education, with the evolution of science and technology, it has become mandatory to provide a highly interactive educational environment and experience using DX technology for residents and medical students, known as digital natives. This study describes an approach to pre- and intraoperative medical education and postoperative rehabilitation using DX in the field of spine surgery that was implemented during the COVID-19 pandemic and will be utilized thereafter.

IgG immune complexes with Staphylococcus aureus protein A enhance osteoclast differentiation and bone resorption by stimulating Fc receptors and TLR2.

Staphylococcus aureus is a main pathogen of osteomyelitis and protein A is a virulence factor with high affinity for IgG. In this study, we investigated whether S. aureus affects the differentiation and bone resorption of osteoclasts through the IgG-binding capacity of protein A. Staphylococcus aureus pre-treated with serum or IgG showed marked enhancement in osteoclastogenesis and bone resorption compared to non-treated S. aureus or a protein A-deficient mutant. Blocking of the Fc receptor and deletion of the Fcγ receptor gene in osteoclast precursor cells showed that enhanced osteoclastogenesis stimulated by S. aureus IgG immune complexes (ICs) was mediated by the Fc receptor on osteoclast precursor cells. In addition, osteoclastogenesis stimulated by S. aureus ICs but not the protein A-deficient mutant was markedly reduced in osteoclast precursor cells of Myd88-knockout mice. Moreover, NFATc1, Syk and NF-κB signals were necessary for osteoclastogenesis stimulated by S. aureus ICs. The results suggest the contribution of a of Toll-like receptor 2 (TLR2)-Myd88 signal to the activity of S. aureus ICs. We further examined the expression of pro-inflammatory cytokines that is known to be enhanced by FcγR-TLR cross-talk. Osteoclasts induced by S. aureus ICs showed higher expression of TNF-α and IL-1ß, and marked stimulation of proton secretion of osteoclasts activated by pro-inflammatory cytokines. Finally, injection of S. aureus, but not the protein A-deficient mutant, exacerbated bone loss in implantation and intra-peritoneal administration mouse models. Our results provide a novel mechanistic aspect of bone loss induced by S. aureus in which ICs and both Fc receptors and TLR pathways are involved.

Periarticular analgesic injection containing a corticosteroid after total hip arthroplasty may prevent deep venous thrombosis: a retrospective comparative cohort study.

BACKGROUND: Of late, periarticular analgesic injection (PAI) has become a common alternative treatment for pain following total hip arthroplasty (THA). However, the systemic effects of PAI containing corticosteroids in patients subjected to THA have not been investigated. This study evaluated the analgesic efficacy and systemic effects of PAI containing a corticosteroid in patients subjected to THA. METHODS: This single-center, retrospective cohort study enrolled patients undergoing unilateral, primary THA. A total of 197 patients (200 hips) were included in the final analyses, with 87 hips in the PAI group and 113 hips in the control group. Numeric Rating Scale (NRS) and laboratory data were assessed preoperatively and on postoperative days (POD) 1 and 7. Pearson's correlation coefficients were obtained to assess the correlations between the D-dimer level on POD 7 and each outcome measure on POD 1. RESULTS: The postoperative white blood cell count (WBC) was significantly higher in the PAI group than in the control group. Postoperative NRS, creatine phosphokinase (CK), and C-reactive protein (CRP) levels were significantly lower in the PAI group. D-dimer levels were significantly lower in the PAI group on POD 7. Postoperative aspartate transaminase (AST), alanine aminotransferase, blood urea nitrogen, and creatinine levels were within reference ranges. D-dimer levels on POD 7 showed a significant negative correlation with WBC on POD 1 (r=-0.4652) and a significant positive correlation with the NRS score and AST, CK, CRP, and D-dimer levels on POD 1 (r = 0.1558, 0.2353, 0.2718, 0.3545, and 0.3359, respectively). CONCLUSIONS: PAI containing a corticosteroid may be an effective treatment for pain and inflammation after THA, and it does not seem to cause drug-induced liver or kidney injury. Moreover, corticosteroid PAI can may accelerate early ambulation, which prevents the elevation of postoperative D-dimer levels, and may reduce the risk of deep venous thrombosis.

Prostate transmembrane protein androgen induced 1 is induced by activation of osteoclasts and regulates bone resorption.

Osteoclasts derived from hematopoietic cells are activated on bone surface. To resorb bone, osteoclasts release acid and lysosome acid hydrolase via membrane transport. Prostate transmembrane protein androgen induced 1 (Pmepa1) is a type I transmembrane protein that regulates proliferation, migration, and metastasis of cancer cells. Because recent reports showed that Pmepa1 is involved in membrane transport in cancer cells, we investigated the role of Pmepa1 in osteoclast function. Pmepa1 expression was barely detected in osteoclasts formed on plastic surfaces in vitro, but was markedly increased in activated osteoclasts formed on calcified matrix. Inhibitors of bone resorption, such as alendronate, bafilomycin A1, and the PI3K inhibitor LY294002, suppressed the expression of Pmepa1 in osteoclasts. Knockdown of Pmepa1 expression impaired bone resorption activity and inhibited formation of a ring-like, actin-rich podosome belt that is essential for osteoclast function. Pmepa1 protein localized to lysosomes in osteoclasts. In addition, in sites of bone destruction observed in rats with adjuvant-induced arthritis, a marked high level of Pmepa1 expression was associated with the osteoclasts' resorbing bone. Our results suggest that Pmepa1 is a critical regulator of bone resorption and is a promising marker for activated osteoclasts and a potential therapeutic target in pathologic bone destruction.-Xu, X., Hirata, H., Shiraki, M., Kamohara, A., Nishioka, K., Miyamoto, H., Kukita, T., Kukita, A. Prostate transmembrane protein androgen induced 1 is induced by activation of osteoclasts and regulates bone resorption.

Deficiency of stress-associated gene Nupr1 increases bone volume by attenuating differentiation of osteoclasts and enhancing differentiation of osteoblasts.

Nuclear protein 1 (NUPR1) is a multifunctional stress-induced protein involved in regulating tumorigenesis, apoptosis, and autophagy. Bone homeostasis is maintained by bone-resorbing osteoclasts and bone-forming osteoblasts and osteocytes. We aimed to determine the role of NUPR1 in bone metabolism. Using microcomputed tomography, we found that mice lacking Nupr1 exhibited increased bone volume. Histologic analysis showed that Nupr1 deficiency decreased osteoclast numbers but increased osteoblast numbers and osteoid formation. In vitro culture of bone marrow macrophages showed that receptor activator of NF-κB ligand-induced osteoclastogenesis was down-regulated in Nupr1-deficient mice. In contrast, primary osteoblasts from Nupr1-deficient mice revealed that proliferation of osteoblasts and expression of bone matrix proteins were markedly enhanced. In addition, expression of autophagy-related genes, formation of autophagosomes, and cell survival were up-regulated in Nupr1-deficient osteoblasts. In contract, deletion of Nupr1 reduced the formation of osteocyte cellular projection, which is an indicator of mature osteocytes. Importantly, we found that the expression of sclerostin (Sost), an inhibitor of bone formation, was down-regulated in the osteoblasts and osteocytes of Nupr1-deficient mice. Conversely, Nupr1 overexpression enhanced Sost expression in primary osteoblasts. Collectively, these results indicate that Nupr1 deficiency increases bone volume by attenuating production of Sost and osteoclastogenesis and enhancing differentiation of osteoblasts.-Shiraki, M., Xu, X., Iovanna, J. L., Kukita, T., Hirata, H., Kamohara, A., Kubota, Y., Miyamoto, H., Mawatari, M., Kukita, A. Deficiency of stress-associated gene Nupr1 increases bone volume by attenuating differentiation of osteoclasts and enhancing differentiation of osteoblasts.

Morphology of size-selected Ptn clusters on CeO2(111).

Supported Pt catalysts and ceria are well known for their application in automotive exhaust catalysts. Size-selected Pt clusters supported on a CeO2(111) surface exhibit distinct physical and chemical properties. We investigated the morphology of the size-selected Ptn (n = 5-13) clusters on a CeO2(111) surface using scanning tunneling microscopy at room temperature. Ptn clusters prefer a two-dimensional morphology for n = 5 and a three-dimensional (3D) morphology for n ≥ 6. We further observed the preference for a 3D tri-layer structure when n ≥ 10. For each cluster size, we quantitatively estimated the relative fraction of the clusters for each type of morphology. Size-dependent morphology of the Ptn clusters on the CeO2(111) surface was attributed to the Pt-Pt interaction in the cluster and the Pt-O interaction between the cluster and CeO2(111) surface. The results obtained herein provide a clear understanding of the size-dependent morphology of the Ptn clusters on a CeO2(111) surface.