BoneKEy reportsPub Date : 2015-09-16eCollection Date: 2015-01-01DOI: 10.1038/bonekey.2015.114
Claire J Watson, Ronald Y Kwon
{"title":"Osteogenic programs during zebrafish fin regeneration.","authors":"Claire J Watson, Ronald Y Kwon","doi":"10.1038/bonekey.2015.114","DOIUrl":"https://doi.org/10.1038/bonekey.2015.114","url":null,"abstract":"<p><p>Recent advances in genomic, screening and imaging technologies have provided new opportunities to examine the molecular and cellular landscape underlying human physiology and disease. In the context of skeletal research, technologies for systems genetics, high-throughput screening and high-content imaging can aid an unbiased approach when searching for new biological, pathological or therapeutic pathways. However, these approaches necessitate the use of specialized model systems that rapidly produce a phenotype, are easy to manipulate, and amenable to optical study, all while representing mammalian bone physiologies at the molecular and cellular levels. The emerging use of zebrafish (Danio rerio) for modeling human disease highlights its potential to accelerate therapeutic and pathway discovery in the mammalian skeleton. In this review, we consider the potential value of zebrafish fin ray regeneration (a rapid, genetically tractable and optically transparent model of intramembranous ossification) as a translational model for such studies. </p>","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"745"},"PeriodicalIF":0.0,"publicationDate":"2015-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/bonekey.2015.114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34046373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BoneKEy reportsPub Date : 2015-09-09eCollection Date: 2015-01-01DOI: 10.1038/bonekey.2015.111
Koen Raymaekers, Steve Stegen, Nick van Gastel, Geert Carmeliet
{"title":"The vasculature: a vessel for bone metastasis.","authors":"Koen Raymaekers, Steve Stegen, Nick van Gastel, Geert Carmeliet","doi":"10.1038/bonekey.2015.111","DOIUrl":"https://doi.org/10.1038/bonekey.2015.111","url":null,"abstract":"<p><p>Emerging evidence indicates that the interactions between tumor cells and the bone microenvironment have a crucial role in the pathogenesis of bone metastasis and that they can influence tumor cell dissemination, quiescence and tumor growth in the bone. The vasculature is known to be critical for primary tumor growth, and anti-angiogenesis drugs are approved for the treatment of certain tumor types. The role of the vasculature in bone metastasis is less well known, but recent evidence shows that blood vessels in the bone are a key component of the local microenvironment for the tumor cells and contribute to the different consecutive phases of bone metastasis. A better insight in the importance of the vasculature for bone metastasis may help develop novel treatment modalities that either slow down tumor growth or, preferably, prevent or cure bone metastasis. </p>","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"742"},"PeriodicalIF":0.0,"publicationDate":"2015-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/bonekey.2015.111","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34512202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BoneKEy reportsPub Date : 2015-09-02eCollection Date: 2015-01-01DOI: 10.1038/bonekey.2015.112
Elizabeth A Zimmermann, Björn Busse, Robert O Ritchie
{"title":"The fracture mechanics of human bone: influence of disease and treatment.","authors":"Elizabeth A Zimmermann, Björn Busse, Robert O Ritchie","doi":"10.1038/bonekey.2015.112","DOIUrl":"10.1038/bonekey.2015.112","url":null,"abstract":"<p><p>Aging and bone diseases are associated with increased fracture risk. It is therefore pertinent to seek an understanding of the origins of such disease-related deterioration in bone's mechanical properties. The mechanical integrity of bone derives from its hierarchical structure, which in healthy tissue is able to resist complex physiological loading patterns and tolerate damage. Indeed, the mechanisms through which bone derives its mechanical properties make fracture mechanics an ideal framework to study bone's mechanical resistance, where crack-growth resistance curves give a measure of the intrinsic resistance to the initiation of cracks and the extrinsic resistance to the growth of cracks. Recent research on healthy cortical bone has demonstrated how this hierarchical structure can develop intrinsic toughness at the collagen fibril scale mainly through sliding and sacrificial bonding mechanisms that promote plasticity. Furthermore, the bone-matrix structure develops extrinsic toughness at much larger micrometer length-scales, where the structural features are large enough to resist crack growth through crack-tip shielding mechanisms. Although healthy bone tissue can generally resist physiological loading environments, certain conditions such as aging and disease can significantly increase fracture risk. In simple terms, the reduced mechanical integrity originates from alterations to the hierarchical structure. Here, we review how human cortical bone resists fracture in healthy bone and how changes to the bone structure due to aging, osteoporosis, vitamin D deficiency and Paget's disease can affect the mechanical integrity of bone tissue. </p>","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"743"},"PeriodicalIF":0.0,"publicationDate":"2015-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4562496/pdf/bonekey2015112.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34080350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BoneKEy reportsPub Date : 2015-08-26eCollection Date: 2015-01-01DOI: 10.1038/bonekey.2015.100
Itamar Levinger, Tara C Brennan-Speranza, George Jerums, Nigel K Stepto, Fabio R Serpiello, Glenn K McConell, Mitchell Anderson, David L Hare, Elizabeth Byrnes, Peter R Ebeling, Ego Seeman
{"title":"The effect of hyperinsulinaemic-euglycaemic clamp and exercise on bone remodeling markers in obese men.","authors":"Itamar Levinger, Tara C Brennan-Speranza, George Jerums, Nigel K Stepto, Fabio R Serpiello, Glenn K McConell, Mitchell Anderson, David L Hare, Elizabeth Byrnes, Peter R Ebeling, Ego Seeman","doi":"10.1038/bonekey.2015.100","DOIUrl":"https://doi.org/10.1038/bonekey.2015.100","url":null,"abstract":"<p><p>Bone remodelling markers (BRMs) are suppressed following a glucose load and during glucose infusion. As exercise increases indices of bone health and improves glucose handling, we hypothesised that, at rest, hyperinsulinaemic-euglycaemic clamp will suppress BRMs in obese men and that exercise prior to the clamp will prevent this suppression. Eleven obese nondiabetic men (age 58.1±2.2 years, body mass index=33.1±1.4 kg m(-2) mean±s.e.m.) had a hyperinsulinaemic-euglycaemic clamp (HEC) at rest (Control) and 60 min post exercise (four bouts × 4 min cycling at 95% of hazard ratiopeak). Blood samples were analysed for serum insulin, glucose, bone formation markers, total osteocalcin (tOC) and procollagen type 1 N-terminal propeptide (P1NP), and the bone resorption marker, β-isomerised C-terminal telopeptides (β-CTx). In the control trial (no exercise), tOC, P1NP and β-CTx decreased with HEC by >10% compared with baseline (P<0.05). Fasting serum glucose, but not insulin, tended to correlate negatively with the BRMs (β range -0.57 to -0.66, p range 0.051-0.087). β-CTx, but not OC or P1NP, increased within 60 min post exercise (∼16%, P<0.01). During the post-exercise HEC, the glucose infusion rate was ∼30% higher compared with the no exercise trial. Despite this, BRMs were only suppressed to a similar extent as in the control session (10%). HEC suppressed BRMs in obese men. Exercise did not prevent this suppression of BRMs by HEC but improved glucose handling during the trial. It remains to be tested whether an exercise intervention of longer duration may be able to prevent the effect of HEC on bone remodelling. </p>","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"731"},"PeriodicalIF":0.0,"publicationDate":"2015-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549926/pdf/bonekey2015100.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33969008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BoneKEy reportsPub Date : 2015-08-19eCollection Date: 2015-01-01DOI: 10.1038/bonekey.2015.101
Andrea Bonetto, Daniel C Andersson, David L Waning
{"title":"Assessment of muscle mass and strength in mice.","authors":"Andrea Bonetto, Daniel C Andersson, David L Waning","doi":"10.1038/bonekey.2015.101","DOIUrl":"https://doi.org/10.1038/bonekey.2015.101","url":null,"abstract":"<p><p>Muscle weakness is an important phenotype of many diseases that is linked to impaired locomotion and increased mortality. The force that a muscle can generate is determined predominantly by muscle size, fiber type and the excitation-contraction coupling process. Here we describe methods for the histological assessment of whole muscle to determine fiber cross-sectional area and fiber type, determination of changes in myocyte size using C2C12 cells, in vivo functional tests and measurement of contractility in dissected whole muscles. The extensor digitorum longus and soleus muscles are ideally suited for whole-muscle contractility, and dissection of these muscles is described. </p>","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"732"},"PeriodicalIF":0.0,"publicationDate":"2015-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/bonekey.2015.101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33969009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BoneKEy reportsPub Date : 2015-08-19eCollection Date: 2015-01-01DOI: 10.1038/bonekey.2015.97
Robin Michael Delaine-Smith, Behzad Javaheri, Jennifer Helen Edwards, Marisol Vazquez, Robin Mark Howard Rumney
{"title":"Preclinical models for in vitro mechanical loading of bone-derived cells.","authors":"Robin Michael Delaine-Smith, Behzad Javaheri, Jennifer Helen Edwards, Marisol Vazquez, Robin Mark Howard Rumney","doi":"10.1038/bonekey.2015.97","DOIUrl":"https://doi.org/10.1038/bonekey.2015.97","url":null,"abstract":"<p><p>It is well established that bone responds to mechanical stimuli whereby physical forces are translated into chemical signals between cells, via mechanotransduction. It is difficult however to study the precise cellular and molecular responses using in vivo systems. In vitro loading models, which aim to replicate forces found within the bone microenvironment, make the underlying processes of mechanotransduction accessible to the researcher. Direct measurements in vivo and predictive modeling have been used to define these forces in normal physiological and pathological states. The types of mechanical stimuli present in the bone include vibration, fluid shear, substrate deformation and compressive loading, which can all be applied in vitro to monolayer and three-dimensional (3D) cultures. In monolayer, vibration can be readily applied to cultures via a low-magnitude, high-frequency loading rig. Fluid shear can be applied to cultures in multiwell plates via a simple rocking platform to engender gravitational fluid movement or via a pump to cells attached to a slide within a parallel-plate flow chamber, which may be micropatterned for use with osteocytes. Substrate strain can be applied via the vacuum-driven FlexCell system or via a four-point loading jig. 3D cultures better replicate the bone microenvironment and can also be subjected to the same forms of mechanical stimuli as monolayer, including vibration, fluid shear via perfusion flow, strain or compression. 3D cocultures that more closely replicate the bone microenvironment can be used to study the collective response of several cell types to loading. This technical review summarizes the methods for applying mechanical stimuli to bone cells in vitro. </p>","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"728"},"PeriodicalIF":0.0,"publicationDate":"2015-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/bonekey.2015.97","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33969006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BoneKEy reportsPub Date : 2015-08-12eCollection Date: 2015-01-01DOI: 10.1038/bonekey.2015.99
Ernestina Schipani, Laura Mangiavini, Christophe Merceron
{"title":"HIF-1α and growth plate development: what we really know.","authors":"Ernestina Schipani, Laura Mangiavini, Christophe Merceron","doi":"10.1038/bonekey.2015.99","DOIUrl":"https://doi.org/10.1038/bonekey.2015.99","url":null,"abstract":"<p><p>Adaptation to low oxygen tension or hypoxia is a critical event in development and tissue homeostasis. Studies by us and others have shown that the fetal growth plate is an avascular tissue with a gradient of oxygenation, and the transcription factor hypoxia-inducible factor-1α (HIF-1α) is essential for its development. In this brief review, we will summarize our current understanding of the role of HIF-1α in fetal growth plate development, and we will discuss yet unanswered questions in the field of hypoxia and endochondral bone formation. </p>","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"730"},"PeriodicalIF":0.0,"publicationDate":"2015-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/bonekey.2015.99","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33969007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BoneKEy reportsPub Date : 2015-08-05eCollection Date: 2015-01-01DOI: 10.1038/bonekey.2015.77
Peter Burckhardt
{"title":"Calcium revisited, part III: effect of dietary calcium on BMD and fracture risk.","authors":"Peter Burckhardt","doi":"10.1038/bonekey.2015.77","DOIUrl":"10.1038/bonekey.2015.77","url":null,"abstract":"<p><p>Food can be an excellent source of calcium. Dietary calcium is in general as well absorbed as calcium supplements, and exerts the same effects on bone. The main sources are dairy products, but also some vegetables and fruits contain considerable amounts of calcium. Mineral water can serve as a supplement. Cross-sectional, longitudinal and some interventional trials have shown positive effects on bone metabolism, bone density and bone loss. But the effect on fracture incidence is less certain, and that of milk, the most studied dairy product, still unproven. </p>","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"708"},"PeriodicalIF":0.0,"publicationDate":"2015-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c5/d2/bonekey201577.PMC4549924.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34037655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BoneKEy reportsPub Date : 2015-08-05eCollection Date: 2015-01-01DOI: 10.1038/bonekey.2015.98
Vu H Nguyen
{"title":"Osteoporosis-preventive behaviors and their promotion for young men.","authors":"Vu H Nguyen","doi":"10.1038/bonekey.2015.98","DOIUrl":"10.1038/bonekey.2015.98","url":null,"abstract":"<p><p>Osteoporosis in men is a major and neglected public health issue. An experimental study with a sample of 37 young men tested an osteoporosis prevention education intervention to alter osteoporosis health beliefs and to increase osteoporosis-preventive behaviors, in order to determine effectiveness and make public health recommendations. After pretest, control and treatment interventions were administered, with the administration of a posttest 2 weeks later. For all osteoporosis health beliefs and osteoporosis-preventive behaviors measured, no group and time interaction was found to be statistically significant. Both groups had low perceived susceptibility to osteoporosis, low to moderate perceived severity of osteoporosis, high perceived benefits of exercise and calcium to prevent osteoporosis, low perceived barriers to exercise and calcium, and moderate to high levels of confidence in self-efficacy for exercise and calcium. Bouts of exercise per week were adequate; however, consumption of good sources of calcium per day appeared to be low. More research is needed for the promotion of osteoporosis prevention in men. Recommendations promoting preventive behaviors for men have been provided. </p>","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"729"},"PeriodicalIF":0.0,"publicationDate":"2015-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549922/pdf/bonekey201598.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34037656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BoneKEy reportsPub Date : 2015-07-29eCollection Date: 2015-01-01DOI: 10.1038/bonekey.2015.21
Kiyomi Yamazaki, Charis Eng, Sergei A Kuznetsov, John Reinisch, Dennis-Duke Yamashita, John Walker, Craig Cheung, Pamela G Robey, Stephen L-K Yen
{"title":"Missense mutation in the PTEN promoter of a patient with hemifacial hyperplasia.","authors":"Kiyomi Yamazaki, Charis Eng, Sergei A Kuznetsov, John Reinisch, Dennis-Duke Yamashita, John Walker, Craig Cheung, Pamela G Robey, Stephen L-K Yen","doi":"10.1038/bonekey.2015.21","DOIUrl":"https://doi.org/10.1038/bonekey.2015.21","url":null,"abstract":"<p><p>The cellular mechanisms involved in the asymmetric facial overgrowth syndrome, hemifacial hyperplasia (HFH), are not well understood. This study was conducted to compare primary cell cultures from hyperplastic and normal HFH bone for cellular and molecular differences. Primary cultures developed from biopsies of a patient with isolated HFH showed a twofold difference in cell size and cell number between hyperplastic and normal bone. Microarray data suggested a 40% suppression of PTEN (phosphatase-tensin homolog) transcripts. Sequencing of the PTEN gene and promoter identified novel C/G missense mutation (position -1053) in the regulatory region of the PTEN promoter. Western blots of downstream pathway components showed an increase in PKBa/Akt1 phosphorylation and TOR (target of rapamcyin) signal. Sirolimus, an inhibitor of TOR, when added to overgrowth cells reversed the cell size, cell number and total protein differences between hyperplastic and normal cells. In cases of facial overgrowth, which involve PTEN/Akt/TOR dysregulation, sirolimus could be used for limiting cell overgrowth. </p>","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"654"},"PeriodicalIF":0.0,"publicationDate":"2015-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/bonekey.2015.21","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33951482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}