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Aging and disease    2016, Vol. 7 Issue (4) : 514-525     DOI: 10.14336/AD.2015.1206
Review Article |
The Role of Bone Marrow Microenvironment in Governing the Balance between Osteoblastogenesis and Adipogenesis
Li Jiao1,*, Liu Xingyu1, zuo Bin2, Zhang Li3
1Department of Cell Biology, Zunyi Medical College, Zunyi, China
2Department of Orthopedic Surgery, Xinhua Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
3Department of Orthopedics, Tenth People's Hospital, Shanghai Tong Ji University, School of Medicine, Shanghai, China
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In the adult bone marrow, osteoblasts and adipocytes share a common precursor called mesenchymal stem cells (MSCs). The plasticity between the two lineages has been confirmed over the past decades, and has important implications in the etiology of bone diseases such as osteoporosis, which involves an imbalance between osteoblasts and adipocytes. The commitment and differentiation of bone marrow (BM) MSCs is tightly controlled by the local environment that maintains a balance between osteoblast lineage and adipocyte. However, pathological conditions linked to osteoporosis can change the BM microenvironment and shift the MSC fate to favor adipocytes over osteoblasts, and consequently decrease bone mass with marrow fat accumulation. This review discusses the changes that occur in the BM microenvironment under pathological conditions, and how these changes affect MSC fate. We suggest that manipulating local environments could have therapeutic implications to avoid bone loss in diseases like osteoporosis.

Keywords osteoporosis      bone marrow microenvironment      mesenchymal stem cells      osteoblast     
Corresponding Authors: Li Jiao   
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These authors had equal contribution and are designated as co-first authors.

Issue Date: 01 August 2016
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Li Jiao
Liu Xingyu
zuo Bin
Zhang Li
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Li Jiao,Liu Xingyu,zuo Bin, et al. The Role of Bone Marrow Microenvironment in Governing the Balance between Osteoblastogenesis and Adipogenesis[J]. Aging and disease, 2016, 7(4): 514-525.
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Figure 1.  BM microenvironment under pathological conditions. Aging-associated increase in ROS promotes NF-κB releasing from IκB and subsequent translocation into nucleus where it binds to responsive element to activate transcription of inflammatory cytokines such as TNFα, Il-6 and MCP-1. Elevated level of these inflammatory cytokines in BM results in immune cell infiltration from blood, such as T cells, monocytes and macrophages. CD40/CD40L mediated Cell-cell communication between T cells and BM stromal cells further enhances NF-κB signal, promoting stromal cells express more inflammatory cytokines. Additional inflammatory cytokines such as TNFα and IL-1 secreted from stromal cells as well as infiltrated immune cells also stimulates ROS generation through mitochondrial and NADPH oxidase system, forming a positive feedback loop that contributes to BM oxidative stress and chronic inflammation. These pathological environmental signals shift MSC fate to favor adipocytes over osteoblasts. Accumulated fat further deteriorate BM microenvironment through secreted FFAs, inflammatory cytokines and altered adipokine secretome. Besides, excessive FFAs generate more ROS while oxidation, initiating a vicious cycle that accelerates BM microenvironment deterioration.
miR-21Spry1miR-21, positive regulator of osteoblast differentiation by targeting Spry1, is down-regulated by TNFα in OVX mice.[92]
miR-23FasTNFα induces osteoblast apoptosis partly by down-regulating miR-23 expression, which inhibits apoptosis by targeting Fas.[94]
miR-3077-5pHOXA10TNFα promotes miR-3077-5p expression through NF-κB signaling pathway, which then shifts MSCs fate to favor adipocytes over osteoblasts by targeting HOXA10.[93]
miR-705Runx2TNFα promotes miR-705 expression through NF-κB signaling pathway, which then shifts MSCs fate to favor adipocyte over osteoblast by targeting Runx2.[93]
miR-155SOCS1miR-155 was induced in TNFα treated pre-osteoblasts, which then partly mediates the inhibitory effect of TNFα on osteogenesis by targeting SOCS1.[95]
Table 1  miRNAs involved in TNFα-mediated repression of osteoblast differentiation
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