Distinct DNA methylation profiles in bone and blood of osteoporotic and healthy postmenopausal women

Reppe, Sjur; Lien, Tonje G.; Hsu, Yi‐Hsiang; Gautvik, Vigdis T.; Olstad, Ole Kristoffer; Yu, Rona; Bakke, Hege G.; Lyle, Robert; Kringen, Marianne Kristiansen; Glad, Ingrid K.; Gautvik, Kaare M.

doi:10.1080/15592294.2017.1345832

Cited by 65 publications

(67 citation statements)

References 53 publications

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“…Similar to our in vitro studies, the expression of Sost in ex vivo bone organ cultures was increased . Clinical studies inspired by these initial findings demonstrated that Sost/sclerostin expression negatively correlates with DNA methylation at the Sost proximal promoter in several patient populations . In a different set of experiments, we employed ex vivo human bone organ cultures to determine the translatability of findings found in mouse models.…”

Section: Use Of Ex Vivo Bone Organ Cultures For the Study Of Bone Biosupporting

confidence: 69%

“…(62) Clinical studies inspired by these initial findings demonstrated that Sost/sclerostin expression negatively correlates with DNA methylation at the Sost proximal promoter in several patient populations. (63,64) In a different set of experiments, we employed ex vivo human bone organ cultures to determine the translatability of findings found in mouse models. As described previously, PTH increases the expression of Mmp14 in murine bone, which in turn stimulates the production of sRankl.…”

Section: Ex Vivo Bone Organ Cultures As a Bridge To Human Studiesmentioning

confidence: 99%

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Ex Vivo Organ Cultures as Models to Study Bone Biology

Bellido

Delgado‐Calle

2020

JBMR Plus

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The integrity of the skeleton is maintained by the coordinated and balanced activities of the bone cells. Osteoclasts resorb bone, osteoblasts form bone, and osteocytes orchestrate the activities of osteoclasts and osteoblasts. A variety of in vitro approaches has been used in an attempt to reproduce the complex in vivo interactions among bone cells under physiological as well as pathological conditions and to test new therapies. Most cell culture systems lack the proper extracellular matrix, cellular diversity, and native spatial distribution of the components of the bone microenvironment. In contrast, ex vivo cultures of fragments of intact bone preserve key cell–cell and cell–matrix interactions and allow the study of bone cells in their natural 3D environment. Further, bone organ cultures predict the in vivo responses to genetic and pharmacologic interventions saving precious time and resources. Moreover, organ cultures using human bone reproduce human conditions and are a useful tool to test patient responses to therapeutic agents. Thus, these ex vivo approaches provide a platform to perform research in bone physiology and pathophysiology. In this review, we describe protocols optimized in our laboratories to establish ex vivo bone organ cultures and provide technical hints and suggestions. In addition, we present examples on how this technical approach can be employed to study osteocyte biology, drug responses in bone, cancer‐induced bone disease, and cross‐talk between bone and other organs © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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Section: Use Of Ex Vivo Bone Organ Cultures For the Study Of Bone Biosupporting

confidence: 69%

Section: Ex Vivo Bone Organ Cultures As a Bridge To Human Studiesmentioning

confidence: 99%

Ex Vivo Organ Cultures as Models to Study Bone Biology

Bellido

Delgado‐Calle

2020

JBMR Plus

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“…Another study criterion was the use of femoral neck and lumbar spine BMD, and different analytical methods and cut‐off points were used as compared to our study. In another study, change in methylation status in blood of osteoporotic men and women was compared with bone biopsies of osteoporotic subjects . Among 63 CpG identified in bone biopsies, 13 showed correlations with BMD in blood.…”

Section: Discussionmentioning

confidence: 99%

“…Peripheral blood monocytes, which are precursors of bone‐resorbing osteoclasts, secrete several osteoclastogenic cytokines that are implicated in the pathogenesis of OP . Recently, DNA methylation analysis of bone biopsies of postmenopausal women with variable BMD showed differential methylation of CpGs, some of which could be reproduced in blood DNA …”

Section: Introductionmentioning

confidence: 99%

Identification of an Epigenetic Signature of Osteoporosis in Blood DNA of Postmenopausal Women

Cheishvili

Parashar

Mahmood

et al. 2018

Journal of Bone and Mineral Research

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Osteoporosis is one of the most common age-related progressive bone diseases in elderly people. Approximately one in three women and one in five men are predisposed to developing osteoporosis. In postmenopausal women, a reduction in BMD leads to an increased risk of fractures. In the current study, we delineated the DNA methylation signatures in whole blood samples of postmenopausal osteoporotic women. We obtained whole blood DNA from 22 normal women and 22 postmenopausal osteoporotic women (51 to 89 years old) from the Canadian Multicenter Osteoporosis Study (CaMos) cohort. These DNA samples were subjected to Illumina Infinium human methylation 450 K analysis. Illumina 450K raw data were analyzed by Genome Studio software. Analysis of the female participants with early and advanced osteoporosis resulted in the generation of a list of 1233 differentially methylated CpG sites when compared with age-matched normal women. T test, ANOVA, and post hoc statistical analyses were performed, and 77 significantly differentially methylated CpG sites were identified. From the 13 most significant genes, ZNF267, ABLIM2, RHOJ, CDKL5, and PDCD1 were selected for their potential role in bone biology. A weighted polygenic DNA methylation score of these genes predicted osteoporosis at an early stage with high sensitivity and specificity and correlated with measures of bone density. Pyrosequencing analysis of these genes was performed to validate the results obtained from Illumina 450 K methylation analysis. The current study provides proof of principal for the role of DNA methylation in osteoporosis. Using whole blood DNA methylation analysis, women at risk of developing osteoporosis can be identified before a diagnosis of osteoporosis is made using BMD as a screening method. Early diagnosis will help to select patients who might benefit from early therapeutic intervention. © 2018 American Society for Bone and Mineral Research.

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“…Поэтому все чаще возникают проекты, направленные на исследование паттернов ДНКметилирования непо средственно в костном биопсийном материале. Попытка охарактеризовать паттерны метилирования генов, которые значительно ассоциированы с вариабельностью уровня МПКТ у 84 постменопаузальных женщин, была предпри нята в работе (Reppe et al, 2017). Проанализировано более 480 тыс.…”

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The role of DNA methylation in the disorders of bone metabolism

et al. 2019

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Osteoporosis is one of multifactorial diseases, it develops from interactions between the genetic component and the environment. However, the universal epigenetic markers of osteoporosis are not yet defined. Finding the risk factors will predict the risk of osteoporosis at the preclinical stage, help define the course and severity of the disease, and develop preventive measures based on them to reduce the risk of fractures. Expanding knowledge in the field of bone biology, especially in the genetics of osteoporosis and osteoimmunology, showed that osteoporosis is a disease that occurs not only due to hormonal or mechanical disorders, but also as a clinically and genetically heterogeneous disease, and there are still unknown pathogenetic links in its structure. Decreases in bone mass and matrix mineralization as well as changes in bone microarchitecture can have different pathogenetic patterns of development and, moreover, there are unknown links of the pathogenesis of osteoporosis. It is possible that DNA methylation is one of these links and a mechanism for epigenetic regulation of gene expression. Evidence exists that this mechanism alongside regulatory miRNAs and post-translational modifications makes a significant contribution to the central processes of bone remodeling; however, the results of various studies vary greatly, and, therefore, there is a need to understand the significance of the accumulated data and to make them consistent. The purpose of this review is to compile and systematize data on the role of DNA methylation in bone metabolism in normal and pathological conditions, in the formation of osteoporosis, and to assess achievements and trends in this field of research and technologies for studying DNA methylation.

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Distinct DNA methylation profiles in bone and blood of osteoporotic and healthy postmenopausal women

Cited by 65 publications

References 53 publications

Ex Vivo Organ Cultures as Models to Study Bone Biology

Ex Vivo Organ Cultures as Models to Study Bone Biology

Identification of an Epigenetic Signature of Osteoporosis in Blood DNA of Postmenopausal Women

The role of DNA methylation in the disorders of bone metabolism

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