Pub Date : 2015-10-07eCollection Date: 2015-01-01DOI: 10.1038/bonekey.2015.113
Evangelos Terpos, Cyrille B Confavreux, Philippe Clézardin
Skeletal lesions contribute substantially to morbidity and mortality in patients with cancer. The disease manifestation course during metastatic bone disease is driven by tumour cells in the bone marrow, which alter the functions of bone-resorbing (osteoclasts) and bone-forming (osteoblasts) cells, promoting skeletal destruction. Successful therapeutic strategies for the treatment of metastatic bone disease include bisphosphonates and denosumab that inhibit osteoclast-mediated bone resorption. Inhibitors of cathepsin K, Src and activin A are under clinical investigation as potential anti-osteolytics. In this review, we describe current knowledge and future directions of antiresorptive therapies that may reduce or prevent destructive bone lesions from solid tumours and multiple myeloma.
{"title":"Bone antiresorptive agents in the treatment of bone metastases associated with solid tumours or multiple myeloma.","authors":"Evangelos Terpos, Cyrille B Confavreux, Philippe Clézardin","doi":"10.1038/bonekey.2015.113","DOIUrl":"https://doi.org/10.1038/bonekey.2015.113","url":null,"abstract":"<p><p>Skeletal lesions contribute substantially to morbidity and mortality in patients with cancer. The disease manifestation course during metastatic bone disease is driven by tumour cells in the bone marrow, which alter the functions of bone-resorbing (osteoclasts) and bone-forming (osteoblasts) cells, promoting skeletal destruction. Successful therapeutic strategies for the treatment of metastatic bone disease include bisphosphonates and denosumab that inhibit osteoclast-mediated bone resorption. Inhibitors of cathepsin K, Src and activin A are under clinical investigation as potential anti-osteolytics. In this review, we describe current knowledge and future directions of antiresorptive therapies that may reduce or prevent destructive bone lesions from solid tumours and multiple myeloma. </p>","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/bonekey.2015.113","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34193792","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}
Pub Date : 2015-10-07eCollection Date: 2015-01-01DOI: 10.1038/bonekey.2015.117
Noboru Asada, Mari Sato, Yoshio Katayama
The bone contains the bone marrow. The functional communication between bone cells and hematopoiesis has been extensively studied in the past decade or so. Osteolineage cells and their modulators, such as the sympathetic nervous system, macrophages and osteoclasts, form a complex unit to maintain the homeostasis of hematopoiesis, called the 'microenvironment'. Recently, bone-embedded osteocytes, the sensors of gravity and mechanical stress, have joined the microenvironment, and they are demonstrated to contribute to whole body homeostasis through the control of immunity and energy metabolism. The inter-organ communication orchestrated by the bone is summarized in this article.
{"title":"Communication of bone cells with hematopoiesis, immunity and energy metabolism.","authors":"Noboru Asada, Mari Sato, Yoshio Katayama","doi":"10.1038/bonekey.2015.117","DOIUrl":"https://doi.org/10.1038/bonekey.2015.117","url":null,"abstract":"<p><p>The bone contains the bone marrow. The functional communication between bone cells and hematopoiesis has been extensively studied in the past decade or so. Osteolineage cells and their modulators, such as the sympathetic nervous system, macrophages and osteoclasts, form a complex unit to maintain the homeostasis of hematopoiesis, called the 'microenvironment'. Recently, bone-embedded osteocytes, the sensors of gravity and mechanical stress, have joined the microenvironment, and they are demonstrated to contribute to whole body homeostasis through the control of immunity and energy metabolism. The inter-organ communication orchestrated by the bone is summarized in this article. </p>","PeriodicalId":72441,"journal":{"name":"BoneKEy reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/bonekey.2015.117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34125629","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}
Pub Date : 2015-09-16eCollection Date: 2015-01-01DOI: 10.1038/bonekey.2015.114
Claire J Watson, Ronald Y Kwon
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.
{"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":null,"pages":null},"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}
Pub Date : 2015-09-09eCollection Date: 2015-01-01DOI: 10.1038/bonekey.2015.111
Koen Raymaekers, Steve Stegen, Nick van Gastel, Geert Carmeliet
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.
{"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":null,"pages":null},"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}
Pub Date : 2015-09-02eCollection Date: 2015-01-01DOI: 10.1038/bonekey.2015.112
Elizabeth A Zimmermann, Björn Busse, Robert O Ritchie
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.
衰老和骨病与骨折风险增加有关。因此,有必要了解这种与疾病相关的骨骼机械性能退化的根源。骨骼的机械完整性源于其分层结构,健康组织的分层结构能够抵抗复杂的生理负荷模式并承受损伤。事实上,骨骼机械特性的产生机制使断裂力学成为研究骨骼机械阻力的理想框架,其中裂纹生长阻力曲线给出了裂纹产生的内在阻力和裂纹生长的外在阻力。最近对健康皮质骨的研究表明,这种分层结构如何主要通过促进塑性的滑动和牺牲结合机制,在胶原纤维尺度上形成内在韧性。此外,骨基质结构还能在更大的微米长度尺度上形成外在韧性,在这种尺度上,结构特征大到足以通过裂纹尖端屏蔽机制来抵抗裂纹生长。虽然健康的骨组织一般都能抵抗生理负荷环境,但某些情况下,如老化和疾病,会大大增加骨折风险。简单地说,机械完整性的降低源于分层结构的改变。在此,我们将回顾人类皮质骨在健康骨骼中是如何抵抗骨折的,以及由于老化、骨质疏松症、维生素 D 缺乏和 Paget 病而导致的骨结构变化是如何影响骨组织的机械完整性的。
{"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":null,"pages":null},"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}
Pub 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
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.
骨重塑标志物(BRMs)在葡萄糖负荷和葡萄糖输注过程中被抑制。由于运动增加了骨骼健康指数并改善了葡萄糖处理,我们假设,在休息时,高胰岛素-血糖钳钳会抑制肥胖男性的brm,而在钳钳之前的运动可以防止这种抑制。11名肥胖非糖尿病男性(年龄58.1±2.2岁,体重指数=33.1±1.4 kg m(-2平均值±s.e.m))在休息时(对照组)和运动后60分钟(4次× 4分钟骑行,95%危险比)患有高胰岛素血症-血糖钳夹(HEC)。分析血液样本的血清胰岛素、葡萄糖、骨形成标志物、总骨钙素(tOC)和前胶原1型n端前肽(P1NP),以及骨吸收标志物β-异构c端端肽(β-CTx)。在对照试验(无运动)中,tOC、P1NP和β-CTx随HEC下降,与基线相比下降>10%
{"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":null,"pages":null},"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}
Pub Date : 2015-08-19eCollection Date: 2015-01-01DOI: 10.1038/bonekey.2015.101
Andrea Bonetto, Daniel C Andersson, David L Waning
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.
{"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":null,"pages":null},"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}
Pub 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
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.
{"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":null,"pages":null},"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}
Pub Date : 2015-08-12eCollection Date: 2015-01-01DOI: 10.1038/bonekey.2015.99
Ernestina Schipani, Laura Mangiavini, Christophe Merceron
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.
{"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":null,"pages":null},"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}
Pub Date : 2015-08-05eCollection Date: 2015-01-01DOI: 10.1038/bonekey.2015.77
Peter Burckhardt
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.
{"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":null,"pages":null},"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}