BoneKEy reports最新文献_第7页

Adult Tph2 knockout mice without brain serotonin have moderately elevated spine trabecular bone but moderately low cortical bone thickness. 没有脑5 -羟色胺的成年Tph2基因敲除小鼠脊柱小梁骨中度升高，但皮质骨厚度中度降低。

BoneKEy reports Pub Date : 2015-07-15 eCollection Date: 2015-01-01 DOI: 10.1038/bonekey.2015.87

Robert Brommage, Jeff Liu, Deon Doree, Wangsheng Yu, David R Powell, Qi Melissa Yang

引用次数: 17

Genetic regulation of bone strength: a review of animal model studies. 骨强度的遗传调控:动物模型研究综述。

BoneKEy reports Pub Date : 2015-07-08 eCollection Date: 2015-01-01 DOI: 10.1038/bonekey.2015.83

Douglas J Adams, Cheryl L Ackert-Bicknell

{"title":"Genetic regulation of bone strength: a review of animal model studies.","authors":"Douglas J Adams, Cheryl L Ackert-Bicknell","doi":"10.1038/bonekey.2015.83","DOIUrl":"https://doi.org/10.1038/bonekey.2015.83","url":null,"abstract":"Population- and family-based studies have established that fragility fracture risk is heritable; yet, the genome-wide association studies published to date have only accounted for a small fraction of the known variation for fracture risk of either the femur or the lumbar spine. Much work has been carried out using animal models toward finding genetic loci that are associated with bone strength. Studies using animal models overcome some of the issues associated with using patient data, but caution is needed when interpreting the results. In this review, we examine the types of tests that have been used for forward genetics mapping in animal models to identify loci and/or genes that regulate bone strength and discuss the limitations of these test methods. In addition, we present a summary of the quantitative trait loci that have been mapped for bone strength in mice, rats and chickens. The majority of these loci co-map with loci for bone size and/or geometry and thus likely dictate strength via modulating bone size. Differences in bone matrix composition have been demonstrated when comparing inbred strains of mice, and these matrix differences may be associated with differences in bone strength. However, additional work is needed to identify loci that act on bone strength at the materials level. ","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"714"},"PeriodicalIF":0.0,"publicationDate":"2015-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/bonekey.2015.83","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34273969","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}

引用次数: 14

TGFβ-Mediated induction of SphK1 as a potential determinant in human MDA-MB-231 breast cancer cell bone metastasis. tgf β介导的SphK1在人MDA-MB-231乳腺癌细胞骨转移中的潜在决定因素

BoneKEy reports Pub Date : 2015-07-08 eCollection Date: 2015-01-01 DOI: 10.1038/bonekey.2015.88

Keith R Stayrook, Justin K Mack, Donna Cerabona, Daniel F Edwards, Hai H Bui, Maria Niewolna, Pierrick Gj Fournier, Khalid S Mohammad, David L Waning, Theresa A Guise

{"title":"TGFβ-Mediated induction of SphK1 as a potential determinant in human MDA-MB-231 breast cancer cell bone metastasis.","authors":"Keith R Stayrook, Justin K Mack, Donna Cerabona, Daniel F Edwards, Hai H Bui, Maria Niewolna, Pierrick Gj Fournier, Khalid S Mohammad, David L Waning, Theresa A Guise","doi":"10.1038/bonekey.2015.88","DOIUrl":"https://doi.org/10.1038/bonekey.2015.88","url":null,"abstract":"Mechanistic understanding of the preferential homing of circulating tumor cells to bone and their perturbation on bone metabolism within the tumor-bone microenvironment remains poorly understood. Alteration in both transforming growth factor β (TGFβ) signaling and sphingolipid metabolism results in the promotion of tumor growth and metastasis. Previous studies using MDA-MB-231 human breast cancer-derived cell lines of variable metastatic potential were queried for changes in sphingolipid metabolism genes to explore correlations between TGFβ dependence and bone metastatic behavior. Of these genes, only sphingosine kinase-1 (SPHK1) was identified to be significantly increased following TGFβ treatment. Induction of SPHK1 expression correlated to the degree of metastatic capacity in these MDA-MB-231-derived cell lines. We demonstrate that TGFβ mediates the regulation of SPHK1 gene expression, protein kinase activity and is critical to MDA-MB-231 cell viability. Furthermore, a bioinformatic analysis of human breast cancer gene expression supports SPHK1 as a hallmark TGFβ target gene that also bears the genetic fingerprint of the basal-like/triple-negative breast cancer molecular subtype. These data suggest a potential new signaling axis between TGFβ/SphK1 that may have a role in the development, prognosis or the clinical phenotype associated with tumor-bone metastasis. ","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"719"},"PeriodicalIF":0.0,"publicationDate":"2015-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/bonekey.2015.88","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34273971","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}

引用次数: 15

The regulation of osteoclast differentiation by Wnt signals. Wnt信号对破骨细胞分化的调控。

BoneKEy reports Pub Date : 2015-07-01 eCollection Date: 2015-01-01 DOI: 10.1038/bonekey.2015.82

Yasuhiro Kobayashi, Shunsuke Uehara, Masanori Koide, Naoyuki Takahashi

{"title":"The regulation of osteoclast differentiation by Wnt signals.","authors":"Yasuhiro Kobayashi, Shunsuke Uehara, Masanori Koide, Naoyuki Takahashi","doi":"10.1038/bonekey.2015.82","DOIUrl":"https://doi.org/10.1038/bonekey.2015.82","url":null,"abstract":"Wnt ligands activate β-catenin-dependent canonical and -independent noncanonical signaling pathways. Wnt regulates many physiological events such as the development of organs and bone metabolism. In contrast, failed signaling leads to pathological conditions including cancer and osteoporosis. Analyses of loss-of-function mutations in the low-density lipoprotein receptor-related protein (Lrp) 5 gene revealed that Lrp5 acted as a co-receptor of Wnt/β-catenin signals and positively regulated bone mass in humans and mice. Many players in Wnt signals including sclerostin, an osteocyte-derived Wnt antagonist, also have since been found to influence bone mass. Bone mass is regulated by the activities of bone-forming osteoblasts, -resorbing osteoclasts and matrix-embedded osteocytes. The roles of Wnt/β-catenin signals in osteoblastogenesis and osteoclastogenesis have been established by the findings of a large number of in vitro and in vivo studies. In contrast, the roles of noncanonical Wnt signals in bone metabolism are only now being examined. In this review, we introduced and discussed recent information on the roles of Wnt signals in bone resorption. ","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"713"},"PeriodicalIF":0.0,"publicationDate":"2015-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/bonekey.2015.82","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34273968","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}

引用次数: 3

Point mutations in an epigenetic factor lead to multiple types of bone tumors: role of H3.3 histone variant in bone development and disease. 一个表观遗传因子的点突变导致多种类型的骨肿瘤:H3.3组蛋白变异在骨发育和疾病中的作用

BoneKEy reports Pub Date : 2015-07-01 eCollection Date: 2015-01-01 DOI: 10.1038/bonekey.2015.84

Shigeaki Kato, Takeaki Ishii, Alexander Kouzmenko

{"title":"Point mutations in an epigenetic factor lead to multiple types of bone tumors: role of H3.3 histone variant in bone development and disease.","authors":"Shigeaki Kato, Takeaki Ishii, Alexander Kouzmenko","doi":"10.1038/bonekey.2015.84","DOIUrl":"https://doi.org/10.1038/bonekey.2015.84","url":null,"abstract":"Coordinated post-translational modifications (PTMs) of nucleosomal histones emerge as a key mechanism of gene regulation by defining chromatin configuration. Patterns of histone modifications vary in different cells and constitute core elements of cell-specific epigenomes. Recently, in addition to canonical histone proteins produced during the S phase of cell cycle, several non-canonical histone variants have been identified and shown to express in a DNA replication-independent manner. These histone variants generate diversity in nucleosomal structures and add further complexity to mechanisms of epigenetic regulation. Cell-specific functions of histone variants remain to be determined. Several recent studies reported an association between some point mutations in the non-canonical histone H3.3 and particular types of brain and bone tumors. This suggests a possibility of differential physiological effects of histone variants in different cells and tissues, including bone. In this review, we outline the roles of histone variants and their PTMs in the epigenetic regulation of chromatin structure and discuss possible mechanisms of biological effects of the non-canonical histone mutations found in bone tumors on tumorigenesis in differentiating bone stem cells. ","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"715"},"PeriodicalIF":0.0,"publicationDate":"2015-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/bonekey.2015.84","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34273970","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}

引用次数: 7

Androgen-deprivation therapy and bone loss in prostate cancer patients: a clinical review. 雄激素剥夺治疗和前列腺癌患者骨质流失:一项临床综述。

BoneKEy reports Pub Date : 2015-06-24 eCollection Date: 2015-01-01 DOI: 10.1038/bonekey.2015.85

Marc Bienz, Fred Saad

{"title":"Androgen-deprivation therapy and bone loss in prostate cancer patients: a clinical review.","authors":"Marc Bienz, Fred Saad","doi":"10.1038/bonekey.2015.85","DOIUrl":"https://doi.org/10.1038/bonekey.2015.85","url":null,"abstract":"Androgen-deprivation therapy (ADT) has become a standard of care in the management of advanced prostate cancer or as an adjunct therapy. However, ADT is associated with a well-known deleterious effect on bone health, resulting in a decrease in bone-mass density (BMD) and increased risk for fracture. With the longer life expectancy of prostate cancer patients, improvement of the quality of life has become increasingly important. Therefore, adequate screening, prevention and treatment of BMD loss is paramount. Zoledronic acid and denosumab have shown promising results in recent studies, which has led to the Food and Drug Administration approval of these treatment options in various settings throughout the course of the disease, including the prevention of ADT-associated bone loss. This review focuses on the various parameters that impact BMD loss in men initiating ADT, on the specific effect of ADT on bone health and on various lifestyle modifications and treatment options such as bisphosphonates, osteoclast-targeted therapy and selective estrogen-receptor modulators that have shown promising results in recent studies. ","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"716"},"PeriodicalIF":0.0,"publicationDate":"2015-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/bonekey.2015.85","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33971526","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}

引用次数: 43

In vivo reference point indentation measurement variability in skeletally mature inbred mice. 骨骼成熟近交系小鼠体内参考点压痕测量变异性。

BoneKEy reports Pub Date : 2015-06-17 eCollection Date: 2015-01-01 DOI: 10.1038/bonekey.2015.81

Andrew Srisuwananukorn, Matthew R Allen, Drew M Brown, Joseph M Wallace, Jason M Organ

{"title":"In vivo reference point indentation measurement variability in skeletally mature inbred mice.","authors":"Andrew Srisuwananukorn, Matthew R Allen, Drew M Brown, Joseph M Wallace, Jason M Organ","doi":"10.1038/bonekey.2015.81","DOIUrl":"https://doi.org/10.1038/bonekey.2015.81","url":null,"abstract":"Reference point indentation (RPI) was developed to measure material-level mechanical properties of bone in vivo. Studies using RPI in vivo have discriminated between human subjects with previous skeletal fractures and those without and among dogs given different anti-remodeling drugs. Recently, this technology was extended to rats, providing the first in vivo data for rodents. The goal of the present study was to perform in vivo RPI measurements in mice, the most common animal model used to study bone. Twelve 16-week-old female C57BL/6 mice were subjected to RPI (three tests) on the anterior tibia, followed by a repeat test session on the contralateral limb 28 days later. A custom MATLAB program was used to derive several outcome parameters from RPI force-displacement curves: first cycle indentation distance (ID-1st), ID increase (IDI), total ID (TID), first cycle unloading slope (US-1st) and first cycle energy dissipation (ED-1st). Data within an individual were averaged across the three tests for each time point. Within-animal variation of all RPI parameters on day 1 ranged from 12.8 to 33.4% and from 14.1 to 22.4% on day 28. Between-animal variation on day 1 ranged from 11.4% to 22.8% and from 7.5% to 24.7% on day 28. At both time points, within- and between-animals, US-1st was the least variable parameter and IDI was most variable. All parameters were nonsignificantly lower at day 28 compared with day 1. These data are important to demonstrate the feasibility of collecting bone material property data longitudinally in mice and will inform the design of future studies in terms of statistical power and appropriate sample size considerations. ","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"712"},"PeriodicalIF":0.0,"publicationDate":"2015-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4478874/pdf/bonekey201581.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33971525","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}

引用次数: 9

Focus on the p38 MAPK signaling pathway in bone development and maintenance. 关注p38 MAPK信号通路在骨发育和维持中的作用。

BoneKEy reports Pub Date : 2015-06-10 eCollection Date: 2015-01-01 DOI: 10.1038/bonekey.2015.80

Cyril Thouverey, Joseph Caverzasio

引用次数: 114

Inflammation and skeletal metastasis. 炎症和骨骼转移。

BoneKEy reports Pub Date : 2015-06-10 eCollection Date: 2015-01-01 DOI: 10.1038/bonekey.2015.75

Hernan Roca, Laurie K McCauley

{"title":"Inflammation and skeletal metastasis.","authors":"Hernan Roca, Laurie K McCauley","doi":"10.1038/bonekey.2015.75","DOIUrl":"https://doi.org/10.1038/bonekey.2015.75","url":null,"abstract":"On the road to metastasis a cancer cell has to overcome two major obstacles: the physical escape from the primary tumor to a distant tissue and the adaptation to the new microenvironment via colonization and the formation of a secondary tumor. Accumulated scientific findings support the hypothesis that inflammation is a critical component of the tumor microenvironment and develops as a result of tumor-induced recruitment of inflammatory cells and their reciprocal interaction with other cells from the tumor network. These interactions modulate immune responses to suppress antitumor immunity and activate feedback amplification signaling loops that link nearly all the cells in the cancer inflammatory milieu. The coordinated regulation of cytokines/chemokines, receptors and other inflammatory mediators enables the different steps of the metastatic cascade. As a target organ for colonization, the bone is rich in inflammatory mediators that are critical for successful cancer growth. In this review, we focus on the inflammatory cells, molecules and mechanisms that facilitate the expansion of cancer cells from the primary tumor to their new 'home' in the skeleton. ","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"706"},"PeriodicalIF":0.0,"publicationDate":"2015-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/bonekey.2015.75","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34251922","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}

引用次数: 28

Dysregulation of phosphate metabolism and conditions associated with phosphate toxicity. 磷酸盐代谢失调和与磷酸盐毒性相关的条件。

BoneKEy reports Pub Date : 2015-06-03 eCollection Date: 2015-01-01 DOI: 10.1038/bonekey.2015.74

Ronald B Brown, Mohammed S Razzaque

{"title":"Dysregulation of phosphate metabolism and conditions associated with phosphate toxicity.","authors":"Ronald B Brown, Mohammed S Razzaque","doi":"10.1038/bonekey.2015.74","DOIUrl":"10.1038/bonekey.2015.74","url":null,"abstract":"Phosphate homeostasis is coordinated and regulated by complex cross-organ talk through delicate hormonal networks. Parathyroid hormone (PTH), secreted in response to low serum calcium, has an important role in maintaining phosphate homeostasis by influencing renal synthesis of 1,25-dihydroxyvitamin D, thereby increasing intestinal phosphate absorption. Moreover, PTH can increase phosphate efflux from bone and contribute to renal phosphate homeostasis through phosphaturic effects. In addition, PTH can induce skeletal synthesis of another potent phosphaturic hormone, fibroblast growth factor 23 (FGF23), which is able to inhibit renal tubular phosphate reabsorption, thereby increasing urinary phosphate excretion. FGF23 can also fine-tune vitamin D homeostasis by suppressing renal expression of 1-alpha hydroxylase (1α(OH)ase). This review briefly discusses how FGF23, by forming a bone-kidney axis, regulates phosphate homeostasis, and how its dysregulation can lead to phosphate toxicity that induces widespread tissue injury. We also provide evidence to explain how phosphate toxicity related to dietary phosphorus overload may facilitate incidence of noncommunicable diseases including kidney disease, cardiovascular disease, cancers and skeletal disorders. ","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"705"},"PeriodicalIF":0.0,"publicationDate":"2015-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/bonekey.2015.74","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34251919","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}

引用次数: 45