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Nuclear factor E2 p45-related factor 2 (Nrf2) is a transcription factor involved in the expression of cytoprotective genes induced by external stresses. We investigated the role of Nrf2 in osteoclast and osteoblast differentiation. Nrf2 knockdown or deletion increased osteoclastic differentiation from bone marrow-derived macrophages (BMMs) through the upregulation of NF-κB, c-Fos, and NFATc1 transcription...
Today, finding an ideal biomaterial to treat the large bone defects, delayed unions and non-unions remains a challenge for orthopedic surgeons and researchers. Several studies have been carried out on the subject of bone regeneration, each having its own advantages. At the same time, a variety of disadvantages still remain. The present study has been designed in vivo to evaluate the effects of osteogenic...
As microenvironmental factors such as three-dimensionality and cell–matrix interactions are increasingly being acknowledged by cancer biologists, more complex 3D in vitro models are being developed to study tumorigenesis and cancer progression. To better understand the pathophysiology of bone metastasis, we have established and validated a 3D indirect co-culture model to investigate the paracrine...
Numerous clinical cohorts are exposed to reduced skeletal loading and associated bone loss, including surgical patients, stroke and spinal cord injury victims, and women on bed rest during pregnancy. In this context, understanding disuse-related bone loss is critical to developing interventions to prevent fractures and the associated morbidity, mortality, and cost to the health care system. The aim...
The data on the association between coffee consumption and the risk of fractures are inconclusive. We performed a comprehensive literature review and meta-analysis to better quantify this association.We identified all potentially relevant articles by searching MEDLINE, EMBASE, Cochrane Library, Web of Science, SCOPUS, and CINAHL (until February 2013). The keywords “coffee,” “caffeine,” “drink,” and...
It has been indicated that both cadmium (Cd) and lead (Pb) may have adverse effects on the bone. However, most studies have only focused on a single factor. The primary and main and interactive effects of Cd and Pb on bone mineral density (BMD) in a Chinese population were observed in this study. A total of 321 individuals (202 women and 119 men), aged 27years and older, living in control and polluted...
Osteosarcoma is the most common primary malignant tumor of bone and accounts for half of all primary skeletal malignancies in children and teenagers. The prognosis for patients who fail or progress on first-line chemotherapy protocols is poor, therefore, additional adjuvant therapeutic strategies are needed. A recent feasibility study has demonstrated that the nitrogen-containing bisphosphonate zoledronic...
The benefits of bisphosphonates are well documented, but prolonged use has been associated with atypical femur fractures. Radiographic markers for fracture predisposition could potentially aid in safer medication use. In this case–control designed study, we compared hip radiographic parameters and the demographic characteristics of chronic bisphosphonate users who sustained an atypical femoral fracture...
Low bone mineral density (BMD) is a risk factor for osteoporosis. Osteoporosis is more prevalent in females than in males. So far, the pathophysiological mechanisms underlying osteoporosis are unclear. Peripheral blood monocytes (PBMs) are precursors of bone-resorbing osteoclasts. This study aims to identify PBM-expressed proteins (genes) influencing hip BMD in humans.We utilized three independent...
High resolution-peripheral quantitative computed tomography (HR-pQCT) measurements are carried out in clinical research protocols to analyze cortical bone. Micro-computed tomography (micro-CT) is a standard tool for ex vivo examination of bone in 3D. The aim of this work was to evaluate cortical measurements derived from HR-pQCT images compared to those from synchrotron radiation (SR) micro-CT in...
Bone remodeling is under complex regulation from nervous, hormonal and local signals, including gut hormones. Among the gut hormones, a role for the glucose-dependent insulinotropic polypeptide (GIP) has been suggested. However, the rapid degradation of GIP in the bloodstream by the ubiquitous enzyme dipeptidyl peptidase-4 (DPP-4) precludes therapeutic use. To circumvent this problem, a series of...
Stimulation of bone formation by PTH is related to mechanosensitivity. The response to PTH treatment in intact bone could therefore be blunted by unloading. We studied the effects of mechanical loading on the response to PTH treatment in bone healing. Most fractures occur in the metaphyses, therefor we used a model for metaphyseal bone injury.One hind leg of 20 male SD rats was unloaded via intramuscular...
The inner enamel region of erupted teeth is known to exhibit higher fracture toughness and crack growth resistance than bulk phase enamel. However, an explanation for this behavior has been hampered by the lack of compositional information for the residual enamel organic matrix. Since enamel-forming ameloblasts are known to express type VII collagen and type VII collagen null mice display abnormal...
Studies of youth athletics and interventions have shown some maintenance of bone mineral content (BMC; g) after cessation of training, but less is known about sustained effects of everyday physical activity (PA). Using a prospective cohort, this report examined potential effects of childhood PA on adolescent BMC. Participants (N=156 boys, 170 girls) had exams at ages 5, 13, and 15. Body size and maturity...
Definition of identical regions between repeated computed tomography (CT) scans is a key factor to monitor changes in bone microarchitecture. In longitudinal studies, accurate determination of the volume of interest (VOI), using three dimensional (3D) registration may improve precision. Therefore, the aim of our study was to investigate the short-term reproducibility of bone geometry, density, microstructure...
Hip fractures are associated with increased mortality and their incidence in Norway is one of the highest worldwide. The aim of this nationwide study was to examine short- and long-term mortality after hip fractures, burden of disease (attributable fraction and potential years of life lost), and time trends in mortality compared to the total Norwegian population. Information on incident hip fractures...
The rising levels of radiation exposure, specifically for medical treatments and accidental exposures, have added great concern for the long term risks of bone fractures. Both the bone marrow and bone architecture are devastated following radiation exposure. Even sub-lethal doses cause a deficit to the bone marrow microenvironment, including a decline in hematopoietic cells, and this deficit occurs...
Bones of the craniofacial skeleton are derived from two distinct cell lineages, cranial neural crest and mesoderm, and articulate at sutures and synchondroses which represent major bone growth sites. Premature fusion of cranial suture(s) is associated with craniofacial dysmorphogenesis caused in part by alteration in the growth potential at sutures and can occur as an isolated birth defect or as part...
High plasma homocysteine levels have been associated with incident osteoporotic fractures, but the mechanisms underlying this association are still unknown. It has been hypothesized that homocysteine might interfere with collagen cross-linking in bone, thereby weakening bone structure. Therefore, we wanted to investigate whether plasma homocysteine levels are associated with bone quality parameters,...
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