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      In Osteoporosis, differentiation of mesenchymal stem cells (MSCs) improves bone marrow adipogenesis

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          Abstract

          The formation, maintenance, and repair of bone tissue involve close interlinks between two stem cell types housed in the bone marrow: the hematologic stem cell originating osteoclasts and mesenchymal stromal cells (MSCs) generating osteoblasts. In this review, we consider malfunctioning of MSCs as essential for osteoporosis. In osteoporosis, increased bone fragility and susceptibility to fractures result from increased osteoclastogenesis and insufficient osteoblastogenesis. MSCs are the common precursors for both osteoblasts and adipocytes, among other cell types. MSCs' commitment towards either the osteoblast or adipocyte lineages depends on suitable regulatory factors activating lineage-specific transcriptional regulators. In osteoporosis, the reciprocal balance between the two differentiation pathways is altered, facilitating adipose accretion in bone marrow at the expense of osteoblast formation; suggesting that under this condition MSCs activity and their microenvironment may be disturbed. We summarize research on the properties of MSCs isolated from the bone marrow of control and osteoporotic post-menopausal women. Our observations indicate that intrinsic properties of MSCs are disturbed in osteoporosis. Moreover, we found that the regulatory conditions in the bone marrow fluid of control and osteoporotic patients are significantly different. These conclusions should be relevant for the use of MSCs in therapeutic applications.

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          Pathogenesis of osteoporosis: concepts, conflicts, and prospects.

          Osteoporosis is a disorder in which loss of bone strength leads to fragility fractures. This review examines the fundamental pathogenetic mechanisms underlying this disorder, which include: (a) failure to achieve a skeleton of optimal strength during growth and development; (b) excessive bone resorption resulting in loss of bone mass and disruption of architecture; and (c) failure to replace lost bone due to defects in bone formation. Estrogen deficiency is known to play a critical role in the development of osteoporosis, while calcium and vitamin D deficiencies and secondary hyperparathyroidism also contribute. There are multiple mechanisms underlying the regulation of bone remodeling, and these involve not only the osteoblastic and osteoclastic cell lineages but also other marrow cells, in addition to the interaction of systemic hormones, local cytokines, growth factors, and transcription factors. Polymorphisms of a large number of genes have been associated with differences in bone mass and fragility. It is now possible to diagnose osteoporosis, assess fracture risk, and reduce that risk with antiresorptive or other available therapies. However, new and more effective approaches are likely to emerge from a better understanding of the regulators of bone cell function.
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            Marrow fat metabolism is linked to the systemic energy metabolism.

            Recent advances in understanding the role of bone in the systemic regulation of energy metabolism indicate that bone marrow cells, adipocytes and osteoblasts, are involved in this process. Marrow adipocytes store significant quantities of fat and produce adipokines, leptin and adiponectin, which are known for their role in the regulation of energy metabolism, whereas osteoblasts produce osteocalcin, a bone-specific hormone that has a potential to regulate insulin production in the pancreas and adiponectin production in fat tissue. Both osteoblasts and marrow adipocytes express insulin receptor and respond to insulin-sensitizing anti-diabetic TZDs in a manner, which tightly links bone with the energy metabolism system. Metabolic profile of marrow fat resembles that of both, white and brown fat, which is reflected by its plasticity in acquiring different functions including maintenance of bone micro-environment. Marrow fat responds to physiologic and pathologic changes in energy metabolism status by changing volume and metabolic activity. This review summarizes available information on the metabolic function of marrow fat and provides hypothesis that this fat depot may acquire multiple roles depending on the local and perhaps systemic demands. These functions may include a role in bone energy maintenance and endocrine activities to serve osteogenesis during bone remodeling and bone healing. Copyright © 2011 Elsevier Inc. All rights reserved.
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              Marrow Fat and the Bone Microenvironment: Developmental, Functional, and Pathological Implications

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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Journal
                bres
                Biological Research
                Biol. Res.
                Sociedad de Biología de Chile (Santiago )
                0716-9760
                2012
                : 45
                : 3
                : 279-287
                Affiliations
                [1 ] Universidad de Chile Chile
                [2 ] Maine Medical Center Research Institute USA
                Article
                S0716-97602012000300009
                10.4067/S0716-97602012000300009
                23283437
                Product
                Product Information: website
                Categories
                BIOLOGY

                General life sciences

                MSCs, osteoporosis, adipogenesis, bone marrow microenvironment

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