BoneKEy reports最新文献_第9页

A new WNT on the bone: WNT16, cortical bone thickness, porosity and fractures. 一种新的骨WNT: WNT16，皮质骨厚度，孔隙度和骨折。

BoneKEy reports Pub Date : 2015-05-13 eCollection Date: 2015-01-01 DOI: 10.1038/bonekey.2015.36

Francesca Gori, Ulf Lerner, Claes Ohlsson, Roland Baron

{"title":"A new WNT on the bone: WNT16, cortical bone thickness, porosity and fractures.","authors":"Francesca Gori, Ulf Lerner, Claes Ohlsson, Roland Baron","doi":"10.1038/bonekey.2015.36","DOIUrl":"https://doi.org/10.1038/bonekey.2015.36","url":null,"abstract":"The last decade has provided abundant data implicating the WNT pathway in bone development and in the regulation of skeletal homeostasis. Rare human mutations together with gain- and loss-of-function approaches in mice have clearly demonstrated that disrupted regulation of this pathway leads to altered bone mass. In addition to these rare human and mice mutations, large population-based genome-wide association studies (GWASs) have identified single-nucleotide polymorphisms in ∼60 loci strongly associated with variations in bone mineral density (BMD) at different skeletal sites. Among the loci/genes identified by BMD GWAS, components of the WNT signaling pathway are numerous and have been shown to contribute to skeletal development and homeostasis. Within the components of WNT signaling, the gene coding for WNT16, one of the 19 WNT ligands of the human genome, has been found strongly associated with specific bone traits such as cortical bone thickness, cortical porosity and fracture risk. Recently, the first functional characterization of Wnt16 has confirmed the critical role of Wnt16 in the regulation of cortical bone mass and bone strength in mice. These reports have extended our understanding of Wnt16 function in bone homeostasis and have not only confirmed the unique association of Wnt16 with cortical bone and fracture susceptibility, as suggested by GWAS in human populations, but have also provided novel insights into the biology of this WNT ligand and the mechanism(s) by which it regulates cortical but not trabecular bone homeostasis. Most interestingly, Wnt16 appears to be a strong anti-resorptive soluble factor acting on both osteoblasts and osteoclast precursors. ","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/bonekey.2015.36","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33190392","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: 64

Tumour-derived miRNAs and bone metastasis. 肿瘤来源的mirna与骨转移。

BoneKEy reports Pub Date : 2015-05-13 eCollection Date: 2015-01-01 DOI: 10.1038/bonekey.2015.56

Martine Croset, Casina Kan, Philippe Clézardin

{"title":"Tumour-derived miRNAs and bone metastasis.","authors":"Martine Croset, Casina Kan, Philippe Clézardin","doi":"10.1038/bonekey.2015.56","DOIUrl":"https://doi.org/10.1038/bonekey.2015.56","url":null,"abstract":"Skeletal metastases are complications of epithelial cancers, among which breast, prostate and lung carcinomas are the most osteotropic. In primary tumours, a subset of cancer cells undergoes epithelial-mesenchymal transition, acquires mobility to migrate into the surrounding stroma and seeds at distant sites to grow. The specific development of bone metastasis requires the recruitment of circulating tumour cells in the bone marrow, their adaptation to survive in the surrounding microenvironment where they alter the functions of osteoclasts and osteoblasts, and hijack signals coming from the bone matrix. Each of the molecular pathways underlining these steps is regulated by multiple factors, through the tight control of genes expressed by cancer cells interacting with cells from the bone microenvironment. In this context, miRNAs can act as master regulators of gene expression to control multiple aspects of bone metastasis formation, including cancer cell escape from the primary tumour site, cancer cell dissemination to bone and invasion of the bone marrow, as well as secondary outgrowth and tumour-stroma cell interactions. In the clinic, specific miRNA signatures have been identified in osteotropic cancer cells, raising the possibility that miRNAs could be used as biomarkers of bone metastasis. The regulatory activity of miRNAs in the bone microenvironment also suggests that miRNAs could be promising therapeutic targets. ","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/bonekey.2015.56","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33190395","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: 37

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

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

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

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, Masahiro Hiasa, Yuki Nagata, Tatsuo Okui, Fletcher A White","doi":"10.1038/bonekey.2015.58","DOIUrl":"https://doi.org/10.1038/bonekey.2015.58","url":null,"abstract":"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. ","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":null,"pages":null},"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

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

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, Evelyn Flynn","doi":"10.1038/bonekey.2015.30","DOIUrl":"https://doi.org/10.1038/bonekey.2015.30","url":null,"abstract":"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. ","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":null,"pages":null},"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, Sasidhar Uppuganti, Alexander J Makowski, Barbara J Rowland, Alyssa R Merkel, Julie A Sterling, Todd L Bredbenner, Daniel S Perrien","doi":"10.1038/bonekey.2015.31","DOIUrl":"https://doi.org/10.1038/bonekey.2015.31","url":null,"abstract":"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%. ","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":null,"pages":null},"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