Dataset Information

Bone Marrow Adipose Tissue Deficiency Increases Disuse-Induced Bone Loss in Male Mice.

ABSTRACT: Bone marrow adipose tissue (MAT) is negatively associated with bone mass. Since osteoblasts and adipocytes are derived from the same precursor cells, adipocyte differentiation may occur at the expense of osteoblast differentiation. We used MAT-deficient KitW/W-v (MAT-) mice to determine if absence of MAT reduced bone loss in hindlimb-unloaded (HU) mice. Male MAT- and wild-type (WT) mice were randomly assigned to a baseline, control or HU group (n?=?10 mice/group) within each genotype and HU groups unloaded for 2 weeks. Femurs were evaluated using micro-computed tomography, histomorphometry and targeted gene profiling. MAT- mice had a greater reduction in bone volume fraction after HU than did WT mice. HU MAT- mice had elevated cancellous bone formation and resorption compared to other treatment groups as well as a unique profile of differentially expressed genes. Adoptive transfer of WT bone marrow-derived hematopoietic stem cells reconstituted c-kit but not MAT in KitW/W-v mice. The MAT- WT???KitW/W-v mice lost cancellous bone following 2 weeks of HU. In summary, results from this study suggest that MAT deficiency was not protective, and was associated with exaggerated disuse-induced cancellous bone loss.

SUBMITTER: Keune JA

PROVIDER: S-EPMC5389344 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Bone Marrow Adipose Tissue Deficiency Increases Disuse-Induced Bone Loss in Male Mice.

Keune Jessica A JA Wong Carmen P CP Branscum Adam J AJ Iwaniec Urszula T UT Turner Russell T RT

Scientific reports 20170412

Bone marrow adipose tissue (MAT) is negatively associated with bone mass. Since osteoblasts and adipocytes are derived from the same precursor cells, adipocyte differentiation may occur at the expense of osteoblast differentiation. We used MAT-deficient Kit<sup>W/W-v</sup> (MAT-) mice to determine if absence of MAT reduced bone loss in hindlimb-unloaded (HU) mice. Male MAT- and wild-type (WT) mice were randomly assigned to a baseline, control or HU group (n = 10 mice/group) within each genotype ...[more]

PMID: 28402337

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Project description:Over the past twenty years, evidence has accumulated that biochemically and spatially defined networks of extracellular matrix, cellular components, and interactions dictate cellular differentiation, proliferation, and function in a variety of tissue and diseases. Modeling in vivo systems in vitro has been undeniably necessary, but when simplified 2D conditions rather than 3D in vitro models are used, the reliability and usefulness of the data derived from these models decreases. Thus, there is a pressing need to develop and validate reliable in vitro models to reproduce specific tissue-like structures and mimic functions and responses of cells in a more realistic manner for both drug screening/disease modeling and tissue regeneration applications. In adipose biology and cancer research, these models serve as physiologically relevant 3D platforms to bridge the divide between 2D cultures and in vivo models, bringing about more reliable and translationally useful data to accelerate benchtop to bedside research. Currently, no model has been developed for bone marrow adipose tissue (BMAT), a novel adipose depot that has previously been overlooked as "filler tissue" but has more recently been recognized as endocrine-signaling and systemically relevant. Herein we describe the development of the first 3D, BMAT model derived from either human or mouse bone marrow (BM) mesenchymal stromal cells (MSCs). We found that BMAT models can be stably cultured for at least 3?months in vitro, and that myeloma cells (5TGM1, OPM2 and MM1S cells) can be cultured on these for at least 2?weeks. Upon tumor cell co-culture, delipidation occurred in BMAT adipocytes, suggesting a bidirectional relationship between these two important cell types in the malignant BM niche. Overall, our studies suggest that 3D BMAT represents a "healthier," more realistic tissue model that may be useful for elucidating the effects of MAT on tumor cells, and tumor cells on MAT, to identify novel therapeutic targets. In addition, proteomic characterization as well as microarray data (expression of >22,000 genes) coupled with KEGG pathway analysis and gene set expression analysis (GSEA) supported our development of less-inflammatory 3D BMAT compared to 2D culture. In sum, we developed the first 3D, tissue-engineered bone marrow adipose tissue model, which is a versatile, novel model that can be used to study numerous diseases and biological processes involved with the bone marrow.

Project description:BACKGROUND:Recent publications about differentiation of stem cells to germ cells have motivated researchers to make new approaches to infertility. In vitro production of germ cells improves understanding differentiation process of male and female germ cells. Due to the problem of using embryonic stem cells (ESC), it's necessary the mentioned cells be replaced with some adult multi-potent stem cells in laboratories. OBJECTIVE:The aim of this study was to obtain germ cells from appropriate source beyond ESC and compare differential potentials of adipocytes derived stem cells (ADMSCs) with bone marrow derived stem cells (BMMSCs). MATERIALS AND METHODS:To find multi-potential entity, after providing purified ADMSCs and BMMSCs, differentiation to osteoblast and adipocyte was confirmed by using appropriate culture medium. To confirm mesenchymal lineage production superficial markers (expression of CD90 and CD44 and non-expression of CD45 and CD31) were investigated by flowcytometry. Then the cells were differentiated to germ cells in inductive medium containing retinoic acid for 7days. To evaluate germ cells characteristic markers [Dazl (Deleted in azoospermia-like), Mvh (Mouse vasa homolog gene), Stra8 (Stimulated by retinoic acid) and Scp3 (Synaptonemal complex protein 3)] flowcytometry, imunoflorescence and real time PCR were used. RESULTS:Both types of cells were able to differentiate into osteoblast and adipocyte cells and presentation of stem cell superficial markers (CD90, CD44) and absence of endothelial and blood cell markers (CD31, CD45) were confirmative The flowcytometry, imunoflorescence and real time PCR results showed remarkable expression of germ cells characteristic markers (Mvh, Dazl, Stra8, and Scp3). CONCLUSION:It was found that although ADMSCs were attained easier and also cultured and differentiated rapidly, germ cell markers were expressed in BMMSCs significantly more than ADMSCs. This article extracted from M.Sc. thesis. (Maryam Hosseinzadeh Shirzeily).

Dataset Information

Bone Marrow Adipose Tissue Deficiency Increases Disuse-Induced Bone Loss in Male Mice.

Publications

Bone Marrow Adipose Tissue Deficiency Increases Disuse-Induced Bone Loss in Male Mice.

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