Shifting in Balance Between Osteogenesis and Adipogenesis Substantially Influences Hematopoiesis

Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
Journal of Molecular Cell Biology (Impact Factor: 6.77). 10/2009; 2(2):61-2. DOI: 10.1093/jmcb/mjp030
Source: PubMed


Adipocytes have been viewed as a space-filler in bone marrow for a long time. However, a recent study (Naveiras et al., 2009. Nature 460, 259-263) shows that adipocytes are microenvironmental components that suppress hematopoiesis under homeostatic and especially stressed conditions.

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    • "The AA BM-MSC have been shown to have an abnormal gene expression profile [7] and abnormal immunological properties [8, 9] indicating a BM-MSC dysfunction in AA. It is also recently reported that adipocytes present in the BM suppress HSC maturation and differentiation and an imbalance between adipogenic and osteogenic differentiation of MSC may substantially influence hematopoiesis [10–12]. Thus, in order to further explore the role of BM-MSC in the disease, we have evaluated their adipogenic and osteogenic differentiation potential in patients with AA. "
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    ABSTRACT: Fatty bone marrow (BM) and defective hematopoiesis are a pathologic hallmark of aplastic anemia (AA). We have investigated adipogenic and osteogenic potential of BM mesenchymal stem cells (BM-MSC) in 10 AA patients (08 males and 02 females) with median age of 37 years (range: 06 to 79 years) and in the same number of age and sex matched controls. It was observed that BM-MSC of AA patients had a morphology, phenotype, and osteogenic differentiation potential similar to control subjects but adipocytes differentiated from AA BM-MSC had a higher density and larger size of lipid droplets and they expressed significantly higher levels of adiponectin and FABP4 genes and proteins as compared to control BM-MSC ( P < 0.01 for both). Thus our data shows that AA BM-MSC have enhanced adipogenicity, which may have an important implication in the pathogenesis of the disease.
    Full-text · Article · Apr 2014 · Stem cell International
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    • "Under physiological conditions in the bone marrow, the balance between adipogenesis and osteogenesis of MSC has to be maintained to prevent diseases such as osteoporosis that occurs due to decreased osteogenic differentiation of MSC [1,4,5]. Since adipocytes and osteocytes are a part of the niche cells in the bone marrow, the balance between osteocytes, adipocytes were found to regulate hematopoiesis and tissue homeostasis [6,7]. Thus, a better understanding of the cell intrinsic changes that occur during MSC differentiation is required for cell therapy and tissue repair. "
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    ABSTRACT: Mesenchymal Stem Cells (MSC) are important candidates for therapeutic applications due to their ex vivo proliferation and differentiation capacity. MSC differentiation is controlled by both intrinsic and extrinsic factors and actin cytoskeleton plays a major role in the event. In the current study, we tried to understand the initial molecular mechanisms and pathways that regulate the differentiation of MSC into osteocytes or adipocytes. We observed that actin modification was important during differentiation and differentially regulated during adipogenesis and osteogenesis. Initial disruption of actin polymerization reduced further differentiation of MSC into osteocytes and osteogenic differentiation was accompanied by increase in ERK1/2 and p38 MAPK phosphorylation. However, only p38 MAPK phosphorylation was down regulated upon inhibition of actin polymerization which as accompanied by decreased CD49E expression. Taken together, our results show that actin modification is a pre-requisite for MSC differentiation into osteocytes and adipocytes and osteogenic differentiation is regulated through p38 MAPK phosphorylation. Thus by modifying their cytoskeleton the differentiation potential of MSC could be controlled which might have important implications for tissue repair and regeneration.
    Full-text · Article · Sep 2013 · Journal of Biomedical Science
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    ABSTRACT: After many decades of neuropeptide research, advances in the field of tachykinins have considerably increased and shown their implications in several physiological processes. In this review we focus on the role of the tachykinins in the regulation of hematopoietic functions. Evidence has shown that neural control of this process is emerging as a significant category in hematopoietic modulation. In the context of this regulation, we discuss the existence of a complex network involving the neurokinin receptors, tachykinins and cytokines. This network is tightly regulated by each of its components.
    Full-text · Article · Apr 2010 · Journal of Receptor, Ligand and Channel Research
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