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Chronic stress, sympathetic activation and skeletal metastasis of breast cancer cells. 慢性压力、交感神经激活和乳腺癌细胞的骨骼转移。
BoneKEy reports Pub Date : 2015-05-13 eCollection Date: 2015-01-01 DOI: 10.1038/bonekey.2015.61
Florent Elefteriou
{"title":"Chronic stress, sympathetic activation and skeletal metastasis of breast cancer cells.","authors":"Florent Elefteriou","doi":"10.1038/bonekey.2015.61","DOIUrl":"10.1038/bonekey.2015.61","url":null,"abstract":"<p><p>Improved detection programs and new therapies significantly improved the 5-year survival rate of women with breast cancer. However, some women still relapse and succumb to cancer because of metastatic disease. In particular, chronically depressed patients do not seem to benefit from newly developed treatments and present with shorter survival. The reason for this association is unclear, but recent cues from preclinical studies point to the possible contribution of neuroendocrine factors generated in response to chronic stress and depression. Retrospective clinical studies also suggest a beneficial effect of sympathetic blockade in terms of less advanced disease at diagnosis, lower cancer-specific mortality, longer disease-free survival and reduced metastasis development and tumor recurrence, especially in patients who have taken propranolol before diagnosis. Therefore, β-blockers or therapies normalizing sympathetic tone might be beneficial as early adjuvant therapies to limit skeletal metastases and growth and eventually to improve prognosis in patients with breast cancers. </p>","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"693"},"PeriodicalIF":0.0,"publicationDate":"2015-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4432778/pdf/bonekey201561.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33190398","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: 0
The role of fetuin-A in mineral trafficking and deposition. 胎儿素a在矿物运输和沉积中的作用。
BoneKEy reports Pub Date : 2015-05-06 eCollection Date: 2015-01-01 DOI: 10.1038/bonekey.2015.39
Michael M X Cai, Edward R Smith, Stephen G Holt
{"title":"The role of fetuin-A in mineral trafficking and deposition.","authors":"Michael M X Cai,&nbsp;Edward R Smith,&nbsp;Stephen G Holt","doi":"10.1038/bonekey.2015.39","DOIUrl":"https://doi.org/10.1038/bonekey.2015.39","url":null,"abstract":"<p><p>Calcium and phosphate are the principle ions involved in the deposition of mineral in the human body. Inhibitors of mineralisation are essential for the prevention of ectopic mineral precipitation and deposition. In the past decade, through in vitro, in vivo and clinical observation studies, we have come to appreciate the importance of fetuin-A (Fet-A), a circulating glycoprotein, in preventing ectopic calcium phosphate mineralisation. Moreover, the detection of Fet-A-containing mineral complex, termed calciprotein particles (CPPs), has provided new ways to assess an individual's calcific risk. The pathophysiological significance of CPPs in disease states is yet to be defined, but it provides an exciting avenue to further our understanding of the development of ectopic mineralisation. </p>","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"672"},"PeriodicalIF":0.0,"publicationDate":"2015-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/bonekey.2015.39","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33190394","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: 54
Preclinical mouse models of osteosarcoma. 骨肉瘤的临床前小鼠模型。
BoneKEy reports Pub Date : 2015-05-06 eCollection Date: 2015-01-01 DOI: 10.1038/bonekey.2015.37
Özge Uluçkan, Aude Segaliny, Sander Botter, Janice M Santiago, Anthony J Mutsaers
{"title":"Preclinical mouse models of osteosarcoma.","authors":"Özge Uluçkan,&nbsp;Aude Segaliny,&nbsp;Sander Botter,&nbsp;Janice M Santiago,&nbsp;Anthony J Mutsaers","doi":"10.1038/bonekey.2015.37","DOIUrl":"https://doi.org/10.1038/bonekey.2015.37","url":null,"abstract":"<p><p>Osteosarcoma is the most common form of primary bone tumors with high prevalence in children. Survival rates of osteosarcoma are low, especially in the case of metastases. Mouse models of this disease have been very valuable in investigation of mechanisms of tumorigenesis, metastasis, as well as testing possible therapeutic options. In this chapter, we summarize currently available mouse models for osteosarcoma and provide detailed methodology for the isolation of cell lines from genetically engineered mouse models (GEMMs), gene modification and tumor cell injection methods, as well as imaging techniques. </p>","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"670"},"PeriodicalIF":0.0,"publicationDate":"2015-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/bonekey.2015.37","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33190393","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: 29
Acidic microenvironment and bone pain in cancer-colonized bone. 癌定殖骨的酸性微环境与骨痛。
BoneKEy reports Pub Date : 2015-05-06 eCollection Date: 2015-01-01 DOI: 10.1038/bonekey.2015.58
Toshiyuki Yoneda, Masahiro Hiasa, Yuki Nagata, Tatsuo Okui, Fletcher A White
{"title":"Acidic microenvironment and bone pain in cancer-colonized bone.","authors":"Toshiyuki Yoneda,&nbsp;Masahiro Hiasa,&nbsp;Yuki Nagata,&nbsp;Tatsuo Okui,&nbsp;Fletcher A White","doi":"10.1038/bonekey.2015.58","DOIUrl":"https://doi.org/10.1038/bonekey.2015.58","url":null,"abstract":"<p><p>Solid cancers and hematologic cancers frequently colonize bone and induce skeletal-related complications. Bone pain is one of the most common complications associated with cancer colonization in bone and a major cause of increased morbidity and diminished quality of life, leading to poor survival in cancer patients. Although the mechanisms responsible for cancer-associated bone pain (CABP) are poorly understood, it is likely that complex interactions among cancer cells, bone cells and peripheral nerve cells contribute to the pathophysiology of CABP. Clinical observations that specific inhibitors of osteoclasts reduce CABP indicate a critical role of osteoclasts. Osteoclasts are proton-secreting cells and acidify extracellular bone microenvironment. Cancer cell-colonized bone also releases proton/lactate to avoid intracellular acidification resulting from increased aerobic glycolysis known as the Warburg effect. Thus, extracellular microenvironment of cancer-colonized bone is acidic. Acidosis is algogenic for nociceptive sensory neurons. The bone is densely innervated by the sensory neurons that express acid-sensing nociceptors. Collectively, CABP is evoked by the activation of these nociceptors on the sensory neurons innervating bone by the acidic extracellular microenvironment created by bone-resorbing osteoclasts and bone-colonizing cancer cells. As current treatments do not satisfactorily control CABP and can elicit serious side effects, new therapeutic interventions are needed to manage CABP. Understanding of the cellular and molecular mechanism by which the acidic extracellular microenvironment is created in cancer-colonized bone and by which the expression and function of the acid-sensing nociceptors on the sensory neurons are regulated would facilitate to develop novel therapeutic approaches for the management of CABP. </p>","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"690"},"PeriodicalIF":0.0,"publicationDate":"2015-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/bonekey.2015.58","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33190396","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: 56
Abaloparatide: a new anabolic therapy on the horizon. 鲍巴肽:一种新的合成代谢疗法。
BoneKEy reports Pub Date : 2015-04-29 eCollection Date: 2015-01-01 DOI: 10.1038/bonekey.2015.28
Felicia Cosman
{"title":"Abaloparatide: a new anabolic therapy on the horizon.","authors":"Felicia Cosman","doi":"10.1038/bonekey.2015.28","DOIUrl":"https://doi.org/10.1038/bonekey.2015.28","url":null,"abstract":"","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"661"},"PeriodicalIF":0.0,"publicationDate":"2015-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/bonekey.2015.28","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33317378","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: 11
Screening for vitamin D deficiency in adults. 筛查成人维生素D缺乏症。
BoneKEy reports Pub Date : 2015-04-29 eCollection Date: 2015-01-01 DOI: 10.1038/bonekey.2015.34
H A Bischoff-Ferrari
{"title":"Screening for vitamin D deficiency in adults.","authors":"H A Bischoff-Ferrari","doi":"10.1038/bonekey.2015.34","DOIUrl":"https://doi.org/10.1038/bonekey.2015.34","url":null,"abstract":"","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"667"},"PeriodicalIF":0.0,"publicationDate":"2015-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/bonekey.2015.34","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33317380","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: 16
Structural differences in epiphyseal and physeal hypertrophic chondrocytes. 骨骺和骨骺增生性软骨细胞的结构差异。
BoneKEy reports Pub Date : 2015-04-29 eCollection Date: 2015-01-01 DOI: 10.1038/bonekey.2015.30
Frederic Shapiro, Evelyn Flynn
{"title":"Structural differences in epiphyseal and physeal hypertrophic chondrocytes.","authors":"Frederic Shapiro,&nbsp;Evelyn Flynn","doi":"10.1038/bonekey.2015.30","DOIUrl":"https://doi.org/10.1038/bonekey.2015.30","url":null,"abstract":"<p><p>We have observed that epiphyseal and physeal hypertrophic chondrocytes in BALB/c mice show considerable differences of light microscopic and ultrastructural appearance, even when the cells are at the same stage of differentiation. In addition, cell structure maintenance improved with tissue preparation controlled for osmolarity and for membrane stabilization using 0.5% ruthenium hexammine trichloride (RHT) for both light microscopy (LM) and electron microscopy (EM) or 0.5% lanthanum nitrate for LM. Physeal hypertrophic chondrocytes showed a gradual increase in size closer to the metaphysis and a change in shape as cells elongated along the long axis. The nucleus remained central, with uniformly dispersed chromatin, and the rough endoplasmic reticulum (RER) was randomly dispersed throughout cytoplasm with little to no presence against the cell membrane. Even the lowermost cells showed thin elongated or dilated cisternae of RER and intact cell membranes. Epiphyseal chondrocytes remained circular to oval with no elongation. Nucleus and RER were positioned as a complete transcellular central nucleocytoplasmic column or as an incomplete bud with RER of the column/bud always continuous with RER peripherally against the intact cell membrane. RER was densely packed with parallel cisternae with adjacent cytoplasm empty of organelles but often filled with circular deposits of moderately electron-dense material consistent with fat. Optimal technique for LM involved fixation using glutaraldehyde (GA) 1.3%, paraformaldehyde (PFA) 1% and RHT 0.5% (mOsm 606) embedded in JB-4 plastic and stained with 0.5% toluidine blue. Optimal technique for EM used fixation with GA 1.3%, PFA 1%, RHT 0.5% and cacodylate buffer 0.03 M (mOsm 511) and post-fixation including 1% osmium tetroxide. These observations lead to the possibility that the same basic cell, the hypertrophic chondrocyte, has differing functional mechanisms at different regions of the developing bone. </p>","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"663"},"PeriodicalIF":0.0,"publicationDate":"2015-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/bonekey.2015.30","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33317379","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: 2
Predicting mouse vertebra strength with micro-computed tomography-derived finite element analysis. 用微计算机层析导出的有限元分析预测小鼠椎体强度。
BoneKEy reports Pub Date : 2015-04-22 eCollection Date: 2015-01-01 DOI: 10.1038/bonekey.2015.31
Jeffry S Nyman, Sasidhar Uppuganti, Alexander J Makowski, Barbara J Rowland, Alyssa R Merkel, Julie A Sterling, Todd L Bredbenner, Daniel S Perrien
{"title":"Predicting mouse vertebra strength with micro-computed tomography-derived finite element analysis.","authors":"Jeffry S Nyman,&nbsp;Sasidhar Uppuganti,&nbsp;Alexander J Makowski,&nbsp;Barbara J Rowland,&nbsp;Alyssa R Merkel,&nbsp;Julie A Sterling,&nbsp;Todd L Bredbenner,&nbsp;Daniel S Perrien","doi":"10.1038/bonekey.2015.31","DOIUrl":"https://doi.org/10.1038/bonekey.2015.31","url":null,"abstract":"<p><p>As in clinical studies, finite element analysis (FEA) developed from computed tomography (CT) images of bones are useful in pre-clinical rodent studies assessing treatment effects on vertebral body (VB) strength. Since strength predictions from microCT-derived FEAs (μFEA) have not been validated against experimental measurements of mouse VB strength, a parametric analysis exploring material and failure definitions was performed to determine whether elastic μFEAs with linear failure criteria could reasonably assess VB strength in two studies, treatment and genetic, with differences in bone volume fraction between the control and the experimental groups. VBs were scanned with a 12-μm voxel size, and voxels were directly converted to 8-node, hexahedral elements. The coefficient of determination or R (2) between predicted VB strength and experimental VB strength, as determined from compression tests, was 62.3% for the treatment study and 85.3% for the genetic study when using a homogenous tissue modulus (E t) of 18 GPa for all elements, a failure volume of 2%, and an equivalent failure strain of 0.007. The difference between prediction and measurement (that is, error) increased when lowering the failure volume to 0.1% or increasing it to 4%. Using inhomogeneous tissue density-specific moduli improved the R (2) between predicted and experimental strength when compared with uniform E t=18 GPa. Also, the optimum failure volume is higher for the inhomogeneous than for the homogeneous material definition. Regardless of model assumptions, μFEA can assess differences in murine VB strength between experimental groups when the expected difference in strength is at least 20%. </p>","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"664"},"PeriodicalIF":0.0,"publicationDate":"2015-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/bonekey.2015.31","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33247658","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: 24
Bone remodeling markers and bone metastases: From cancer research to clinical implications. 骨重塑标志物和骨转移:从癌症研究到临床意义。
BoneKEy reports Pub Date : 2015-04-22 eCollection Date: 2015-01-01 DOI: 10.1038/bonekey.2015.35
Arlindo Ferreira, Irina Alho, Sandra Casimiro, Luís Costa
{"title":"Bone remodeling markers and bone metastases: From cancer research to clinical implications.","authors":"Arlindo Ferreira,&nbsp;Irina Alho,&nbsp;Sandra Casimiro,&nbsp;Luís Costa","doi":"10.1038/bonekey.2015.35","DOIUrl":"https://doi.org/10.1038/bonekey.2015.35","url":null,"abstract":"<p><p>Bone metastasis is a frequent finding in the natural history of several types of cancers. However, its anticipated risk, diagnosis and response to therapy are still challenging to assess in clinical practice. Markers of bone metabolism are biochemical by-products that provide insight into the tumor-bone interaction, with potential to enhance the clinical management of patients with bone metastases. In fact, these markers had a cornerstone role in the development of bone-targeted agents; however, its translation to routine practice is still unclear, as reflected by current international guidelines. In this review, we aimed to capture several of the research and clinical translational challenges regarding the use of bone metabolism markers that we consider relevant for future research in bone metastasis. </p>","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"668"},"PeriodicalIF":0.0,"publicationDate":"2015-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/bonekey.2015.35","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33247660","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: 46
Bone marrow stroma-derived miRNAs as regulators, biomarkers and therapeutic targets of bone metastasis. 骨髓基质衍生的 miRNA 是骨转移的调节因子、生物标志物和治疗靶标。
BoneKEy reports Pub Date : 2015-04-15 eCollection Date: 2015-01-01 DOI: 10.1038/bonekey.2015.38
Maša Alečković, Yibin Kang
{"title":"Bone marrow stroma-derived miRNAs as regulators, biomarkers and therapeutic targets of bone metastasis.","authors":"Maša Alečković, Yibin Kang","doi":"10.1038/bonekey.2015.38","DOIUrl":"10.1038/bonekey.2015.38","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) are short, endogenous RNA molecules that have essential roles in regulating gene expression. They control numerous physiological and cellular processes, including normal bone organogenesis and homeostasis, by enhancing or inhibiting bone marrow cell growth, differentiation, functional activity and crosstalk of the multiple cell types within the bone. Hence, elucidating miRNA targets in bone marrow stromal cells has revealed novel regulations during bone development and maintenance. Moreover, recent studies have detailed the capacity for bone stromal miRNAs to influence bone metastasis from a number of primary carcinomas by interfering with bone homeostasis or by directly influencing metastatic tumor cells. Owing to the current lack of good diagnostic biomarkers of bone metastases, such changes in bone stromal miRNA expression in the presence of metastatic lesions may become useful biomarkers, and may even serve as therapeutic targets. In particular, cell-free and exosomal miRNAs shed from bone stromal cells into circulation may be developed into novel biomarkers that can be routinely measured in easily accessible samples. Taken together, these findings reveal the significant role of bone marrow stroma-derived miRNAs in the regulation of bone homeostasis and bone metastasis. </p>","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"671"},"PeriodicalIF":0.0,"publicationDate":"2015-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4398005/pdf/bonekey201538.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33247661","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: 0
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