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Bone Marrow Adipose Tissue: Regulation of Osteoblastic Niche, Hematopoiesis and Hematological Malignancies

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Abstract

Bone marrow adipose tissue (BMAT) creates a specific microniche within multifunctional bone marrow (BM) ecosystem which imposes changes in surrounding cells and at systemic level. Moreover, BMAT contributes to spatial and temporal separation and metabolic compartmentalization of BM, thus regulating BM homeostasis and diseases. Recent findings have identified novel progenitor subsets of bone marrow adipocytes (BMAd)s recruited during the BM adipogenesis within different skeletal and hematopoietic stem cell niches. Potential of certain mesenchymal BM cells to differentiate into both osteogenic and adipogenic lineages, contributes to the complex interplay of BMAT with endosteal (osteoblastic) niche compartments as an important cellular player in bone tissue homeostasis. Targeting and ablation of BMAT cells at certain states might be an optional and promising strategy for improvement of bone health. Additionally, recent findings demonstrated spatial distribution of BMAds related to hematopoietic cells and pointed out important functional roles in the vital processes such as long-term hematopoiesis. BM adipogenesis appears to be an emergency phenomenon that follows the production of hematopoietic stem and progenitor cell niche factors, thus regulating physiological, stressed, and malignant hematopoiesis. Lipolytic and secretory activity of BMAds can influence survival and proliferation of hematopoietic cells at different maturation stages. Due to their different lipid status, constitutive and regulated BMAds are important determinants of normal and malignant hematopoietic cells. Further elucidation of cellular and molecular players involved in BMAT expansion and crosstalk with malignant cells is of paramount importance for conceiving the new therapies for improvement of BM health.

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Data Availability

All data and conclusions generated during this review are included in this published article.

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Abbreviations

BMAT:

AdipoQ: adiponectin

ALL:

Acute lymphobastic leukemia

AML:

Acute myeloid leukemia

Arg 1:

Arginase 1

AT:

Adipose tissue

ATGL:

Adipose triglyceride lipase

BM:

Bone marrow

BMAd:

Bone marrow adipocyte

BMAT:

Bone marrow adipose tissue

BMI1:

Polycomb group protein

BMSC:

BM mesenchymal stromal cell

cBMAd:

Constitutive bone marrow adipocytes

Cebp-ɑ:

CCAAT/enhancer-binding protein a

CFU-GM:

Colony-forming unit-granulocyte–macrophage

CLP:

common lymphoid progenitor

CMP:

Common myeloid progenitor

CR:

Caloric restriction

CXCL12:

C-X-C Motif Chemokine Ligand 12

DTR:

Diphtheria toxin receptor

EPO:

Erythropoietin

FA:

Fatty acids

Fabp4:

Fatty acid binding protein 4

FOXC1:

Forkhead box C1

G-CSF:

Granulocyte colony stimulating factor

HFD:

High fat diet

HSC:

Hematopoietic stem cell

HSL:

Hormon-sensitive lipase

HSPC:

Hematopoietic stem and progenitor cell

IGF-1:

Insulin-like growth factor 1

IL-6:

Interleukin-6

iNOS:

Inducible NO synthase

lcnRNA:

Long non-coding RNA

LT-HSC:

Long term hematopoietic stem cell

MALP:

Marrow adipogenic lineage precursor

MCP-1:

Monocyte chemoattractant protein-1

MDS:

Myelodisplastic syndrome

MM:

Multiple myeloma

OPG:

Osteoprotegerin

PET/CT:

Positron emission tomography–computed tomography

PI3K:

Phosphatidylinositol 3-kinase

Plin1:

Perilipin 1

Pparγ:

Peroxisome proliferator- activated receptor

PRDM1:

PR/SET domain 1

PTH:

Parathyroid hormone

RANK:

Receptor activator of nuclear factor kappa-Β

RANKL:

Receptor activator of nuclear factor kappa-Β ligand

rBMAd:

Regulated bone marrow adipocytes

Runx2:

Runt-related transcription factor 2

sc:

Single cell

SCF:

Stem cell growth factor

SDF-1:

Stromal cell-derived factor 1

T-ALL:

T cells Acute Lymphobastic leukemia

T2DM:

Type 2 diabetes mellitus

TNF-α:

Tumor necrosis factor ɑ

WAT:

White adipose tissue

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DT work is supported by the Ministry of Education, Science and Technological Development of Republic of Serbia [contract number 451–03-68/2022–14/200015 with Institute for Medical Research University of Belgrade, National Institute of Republic of Serbia] and the returning expert program by the Deutsche Gesellschaft für Internationale Zusammenarbeit (GIZ) on behalf of the German Federal Ministry for Economic Cooperation and Development (BMZ).

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  1. Department of Physiology and Cellular Biophysics, Columbia University, New York, NY, USA

    Rossella Labella

  2. Institute for Orthopedy Banjica, Belgrade, Serbia

    Marko Vujačić

  3. Group for Hematology and Stem Cells, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, Dr Subotića 4, POB 39 102, 11129, Belgrade, Serbia

    Drenka Trivanović

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DT conceived the topic. RL, DT and MV wrote the manuscript. DT and RL revised and edited the article. All authors gave final approval.

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Labella, R., Vujačić, M. & Trivanović, D. Bone Marrow Adipose Tissue: Regulation of Osteoblastic Niche, Hematopoiesis and Hematological Malignancies. Stem Cell Rev and Rep 19, 1135–1151 (2023). https://doi.org/10.1007/s12015-023-10531-3

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