BoneKEy reports最新文献_第10页

Bone specific immunity and its impact on metastasis. 骨特异性免疫及其对转移的影响。

BoneKEy reports Pub Date : 2015-04-15 eCollection Date: 2015-01-01 DOI: 10.1038/bonekey.2015.32

Nikola Baschuk, Jay Rautela, Belinda S Parker

{"title":"Bone specific immunity and its impact on metastasis.","authors":"Nikola Baschuk, Jay Rautela, Belinda S Parker","doi":"10.1038/bonekey.2015.32","DOIUrl":"https://doi.org/10.1038/bonekey.2015.32","url":null,"abstract":"Bone is one of the most common sites of metastasis in solid malignancy. Contributing to this osteotropism are the dynamic interactions between tumor cells and the numerous cell types resident in the normal bone, particularly osteoclasts and osteoblasts, which create a tumor supporting microenvironment. However, disseminated cells are detected in the bone marrow long before evidence of metastatic outgrowth, and it is likely that prolonged survival is also reliant on immunoescape. Compared with other peripheral organs such as the lung and spleen, the bone marrow constitutes a unique immune cell compartment that likely provides an immune privileged niche for disseminated tumor cells. This includes the large proportions of immunosuppressive cells, including myeloid derived suppressor cells and regulatory T cells, that blunt the activity of cytotoxic lymphocytes involved in tumor immunosurveillance. This review highlights key aspects of the osteoimmune landscape and emerging mechanisms by which tumor cells create or co-opt an immunosuppressed niche to support their outgrowth in bone. Future studies in this field are likely to shed light on the differences in immunoregulation between the bone and other sites including the primary tumor, and the potential for immunotherapeutics in treating disseminated disease in the bone. However, more immunocompetent models, that recapitulate tumor heterogeneity and bone metastasis need to be developed to accelerate this field. ","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"665"},"PeriodicalIF":0.0,"publicationDate":"2015-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/bonekey.2015.32","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33247659","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: 41

Assessment of bone vascularization and its role in bone remodeling. 评估骨血管化及其在骨重塑中的作用。

BoneKEy reports Pub Date : 2015-04-08 eCollection Date: 2015-01-01 DOI: 10.1038/bonekey.2015.29

Marie-Hélène Lafage-Proust, Bernard Roche, Max Langer, Damien Cleret, Arnaud Vanden Bossche, Thomas Olivier, Laurence Vico

引用次数: 111

Role of syndecan-2 in osteoblast biology and pathology. syndecan-2在成骨细胞生物学和病理学中的作用。

BoneKEy reports Pub Date : 2015-04-01 eCollection Date: 2015-01-01 DOI: 10.1038/bonekey.2015.33

Rafik Mansouri, Eric Haÿ, Pierre J Marie, Dominique Modrowski

引用次数: 21

Molecular alterations that drive breast cancer metastasis to bone. 导致乳腺癌骨转移的分子改变。

BoneKEy reports Pub Date : 2015-03-18 eCollection Date: 2015-01-01 DOI: 10.1038/bonekey.2015.10

Penelope D Ottewell, Liam O'Donnell, Ingunn Holen

{"title":"Molecular alterations that drive breast cancer metastasis to bone.","authors":"Penelope D Ottewell, Liam O'Donnell, Ingunn Holen","doi":"10.1038/bonekey.2015.10","DOIUrl":"https://doi.org/10.1038/bonekey.2015.10","url":null,"abstract":"Epithelial cancers including breast and prostate commonly progress to form incurable bone metastases. For this to occur, cancer cells must adapt their phenotype and behaviour to enable detachment from the primary tumour, invasion into the vasculature, and homing to and subsequent colonisation of bone. It is widely accepted that the metastatic process is driven by the transformation of cancer cells from a sessile epithelial to a motile mesenchymal phenotype through epithelial-mesenchymal transition (EMT). Dissemination of these motile cells into the circulation provides the conduit for cells to metastasise to distant organs. However, accumulating evidence suggests that EMT is not sufficient for metastasis to occur and that specific tissue-homing factors are required for tumour cells to lodge and grow in bone. Once tumour cells are disseminated in the bone environment, they can revert into an epithelial phenotype through the reverse process of mesenchymal-epithelial transition (MET) and form secondary tumours. In this review, we describe the molecular alterations undertaken by breast cancer cells at each stage of the metastatic cascade and discuss how these changes facilitate bone metastasis. ","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"643"},"PeriodicalIF":0.0,"publicationDate":"2015-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/bonekey.2015.10","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33194628","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: 35

Bone microdamage, remodeling and bone fragility: how much damage is too much damage? 骨微损伤、骨重塑与骨脆性:多大程度的损伤才算过度损伤?

BoneKEy reports Pub Date : 2015-03-18 eCollection Date: 2015-01-01 DOI: 10.1038/bonekey.2015.11

Zeynep Seref-Ferlengez, Oran D Kennedy, Mitchell B Schaffler

{"title":"Bone microdamage, remodeling and bone fragility: how much damage is too much damage?","authors":"Zeynep Seref-Ferlengez, Oran D Kennedy, Mitchell B Schaffler","doi":"10.1038/bonekey.2015.11","DOIUrl":"https://doi.org/10.1038/bonekey.2015.11","url":null,"abstract":"Microdamage resulting from fatigue or 'wear and tear' loading contributes to bone fragility; however, the full extent of its influence is not completely understood. Linear microcracks (∼50-100 μm) and diffuse damage (clusters of sublamellar-sized cracks) are the two major bone microdamage types, each with different mechanical and biological consequences. Healthy bone, due to its numerous microstructural interfaces and its ability to affect matrix level repair, deals effectively with microdamage. From a material standpoint, healthy bone behaves much like engineering composites like carbon-fiber reinforced plastics. Both materials allow matrix damage to form during fatigue loading and use microstructural interfaces to dissipate energy and limit microcrack propagation to slow fracture. The terms fracture toughness and 'toughening mechanism', respectively, describe mechanical behavior and microstructural features that prevent crack growth and make it harder to fracture a material. Critically, toughness is independent of strength. In bone, primary toughening features include mineral and collagen interfaces, lamellae and tissue heterogeneity among osteons. The damage tolerance of bone and other composites can be overcome with sustained loading and/or matrix changes such that the microstructure no longer limits microcrack propagation. With reduced remodeling due to aging, disease or remodeling suppression, microdamage accumulation can occur along with loss of tissue heterogeneity. Both contribute additively to reduced fracture toughness. Thus, the answer to the key question for bone fragility of how much microdamage is too much is extremely complex. It ultimately depends on the interplay between matrix damage content, internal repair and effectiveness of matrix-toughening mechanisms. ","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"644"},"PeriodicalIF":0.0,"publicationDate":"2015-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/bonekey.2015.11","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33194629","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: 102

Exercise prevents β-aminopropionitrile-induced morphological changes to type I collagen in murine bone. 运动可防止β-氨基丙腈诱导的小鼠骨I型胶原的形态学改变。

BoneKEy reports Pub Date : 2015-03-11 eCollection Date: 2015-01-01 DOI: 10.1038/bonekey.2015.12

Max A Hammond, Joseph M Wallace

{"title":"Exercise prevents β-aminopropionitrile-induced morphological changes to type I collagen in murine bone.","authors":"Max A Hammond, Joseph M Wallace","doi":"10.1038/bonekey.2015.12","DOIUrl":"https://doi.org/10.1038/bonekey.2015.12","url":null,"abstract":"This study evaluated the effects of reduced enzymatic crosslinking, exercise and the ability of exercise to prevent the deleterious impact of reduced crosslinking on collagen D-spacing. Eight-week-old female mice were divided into four weight-matched groups receiving daily injections of either phosphate-buffered saline (PBS) or 300 mg kg(-1) β-aminopropionitrile (BAPN) while undergoing normal cage activity (Sed) or 30 min per day of treadmill exercise (Ex) for 21 consecutive days. BAPN caused a downward shift in the D-spacing distribution in Sed BAPN compared with Sed PBS (P<0.001) but not in Ex BAPN (P=0.429), indicating that exercise can prevent changes in collagen morphology caused by BAPN. Exercise had no effect on D-spacing in PBS control mice (P=0.726), which suggests that exercise-induced increases in lysyl oxidase may be a possible mechanism for preventing BAPN-induced changes in D-spacing. The D-spacing changes were accompanied by an increase in mineral crystallinity/maturity due to the main effect of BAPN (P=0.016). However, no changes in nanoindentation, reference point indentation or other Raman spectroscopy parameters were observed. The ability of exercise to rescue BAPN-driven changes in collagen morphology necessitates further research into the use of mechanical stimulation as a preventative therapy for collagen-based diseases. ","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"645"},"PeriodicalIF":0.0,"publicationDate":"2015-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/bonekey.2015.12","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33152067","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: 21

Chondrodysplasias and TGFβ signaling. 软骨发育不良和TGFβ信号传导。

BoneKEy reports Pub Date : 2015-03-11 eCollection Date: 2015-01-01 DOI: 10.1038/bonekey.2015.9

Carine Le Goff, Valerie Cormier-Daire

引用次数: 6

HIV infection and osteoporosis. 艾滋病毒感染与骨质疏松症

BoneKEy reports Pub Date : 2015-02-11 eCollection Date: 2015-01-01 DOI: 10.1038/bonekey.2015.3

Juliet Compston

引用次数: 0

Long-term safety of antiresorptive treatment: bone material, matrix and mineralization aspects. 抗骨吸收治疗的长期安全性:骨材料、基质和矿化方面。

BoneKEy reports Pub Date : 2015-02-11 eCollection Date: 2015-01-01 DOI: 10.1038/bonekey.2015.1

Barbara M Misof, Nadja Fratzl-Zelman, Eleftherios P Paschalis, Paul Roschger, Klaus Klaushofer

{"title":"Long-term safety of antiresorptive treatment: bone material, matrix and mineralization aspects.","authors":"Barbara M Misof, Nadja Fratzl-Zelman, Eleftherios P Paschalis, Paul Roschger, Klaus Klaushofer","doi":"10.1038/bonekey.2015.1","DOIUrl":"https://doi.org/10.1038/bonekey.2015.1","url":null,"abstract":"It is well established that long-term antiresorptive use is effective in the reduction of fracture risk in high bone turnover osteoporosis. Nevertheless, during recent years, concerns emerged that longer bone turnover reduction might favor the occurrence of fatigue fractures. However, the underlying mechanisms for both beneficial and suspected adverse effects are not fully understood yet. There is some evidence that their effects on the bone material characteristics have an important role. In principle, the composition and nanostructure of bone material, for example, collagen cross-links and mineral content and crystallinity, is highly dependent on tissue age. Bone turnover determines the age distribution of the bone structural units (BSUs) present in bone, which in turn is decisive for its intrinsic material properties. It is noteworthy that the effects of bone turnover reduction on bone material were observed to be dependent on the duration of the antiresorptive therapy. During the first 2-3 years, significant decreases in the heterogeneity of material properties such as mineralization of the BSUs have been observed. In the long term (5-10 years), the mineralization pattern reverts towards normal heterogeneity and degree of mineralization, with no signs of hypermineralization in the bone matrix. Nevertheless, it has been hypothesized that the occurrence of fatigue fractures (such as atypical femoral fractures) might be linked to a reduced ability of microdamage repair under antiresorptive therapy. The present article examines results from clinical studies after antiresorptive, in particular long-term, therapy with the aforementioned potentially positive or negative effects on bone material. ","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"634"},"PeriodicalIF":0.0,"publicationDate":"2015-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/bonekey.2015.1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33077771","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: 10

Big data challenges in bone research: genome-wide association studies and next-generation sequencing. 骨研究中的大数据挑战:全基因组关联研究和下一代测序。

BoneKEy reports Pub Date : 2015-02-11 eCollection Date: 2015-01-01 DOI: 10.1038/bonekey.2015.2

Nerea Alonso, Gavin Lucas, Pirro Hysi

{"title":"Big data challenges in bone research: genome-wide association studies and next-generation sequencing.","authors":"Nerea Alonso, Gavin Lucas, Pirro Hysi","doi":"10.1038/bonekey.2015.2","DOIUrl":"https://doi.org/10.1038/bonekey.2015.2","url":null,"abstract":"Genome-wide association studies (GWAS) have been developed as a practical method to identify genetic loci associated with disease by scanning multiple markers across the genome. Significant advances in the genetics of complex diseases have been made owing to advances in genotyping technologies, the progress of projects such as HapMap and 1000G and the emergence of genetics as a collaborative discipline. Because of its great potential to be used in parallel by multiple collaborators, it is important to adhere to strict protocols assuring data quality and analyses. Quality control analyses must be applied to each sample and each single-nucleotide polymorphism (SNP). The software package PLINK is capable of performing the whole range of necessary quality control tests. Genotype imputation has also been developed to substantially increase the power of GWAS methodology. Imputation permits the investigation of associations at genetic markers that are not directly genotyped. Results of individual GWAS reports can be combined through meta-analysis. Finally, next-generation sequencing (NGS) has gained popularity in recent years through its capacity to analyse a much greater number of markers across the genome. Although NGS platforms are capable of examining a higher number of SNPs compared with GWA studies, the results obtained by NGS require careful interpretation, as their biological correlation is incompletely understood. In this article, we will discuss the basic features of such protocols. ","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":" ","pages":"635"},"PeriodicalIF":0.0,"publicationDate":"2015-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/bonekey.2015.2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33078207","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: 12