Osteoblast–adipocyte lineage plasticity in tissue development, maintenance and pathology
Department of Developmental Biology, REB 413, Harvard School of Dental Medicine, 188 Longwood Ave, Boston, MA, 02115, USA, .Cellular and Molecular Life Sciences CMLS (Impact Factor: 5.81). 08/2013; 71(3). DOI: 10.1007/s00018-013-1440-z
Osteoblasts and adipocytes share a common precursor in adult bone marrow and there is a degree of plasticity between the two cell lineages. This has important implications for the etiology of not only osteoporosis but also several other diseases involving an imbalance between osteoblasts and adipocytes. Understanding the process of differentiation of osteoblasts and adipocytes and their trans-differentiation is crucial in order to identify genes and other factors that may contribute to the pathophysiology of such diseases. Several transcriptional regulators have been shown to control osteoblast and adipocyte differentiation and function. Regulation of cell commitment occurs at the level of the progenitor cell through cross talk between complex signaling pathways and epigenetic mechanisms such as DNA methylation, chromatin remodeling, and microRNAs. Here we review the complex precursor cell microenvironment controlling osteoblastogenesis and adipogenesis during tissue development, maintenance, and pathology.
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- "The interaction between adipocytes and osteoblasts has traditionally been considered as mutually exclusive such that the transcription factors that induce osteoblastogenesis inhibit adipogenesis and vice versa . Interestingly, there is a significant degree of lineage plasticity between adipocytes and osteoblasts, which share a common progenitor, that further complicates dissecting the relationship between these two cell types in healthy and cancer-containing bone marrow  . Recent evidence suggests, however, that bone marrow adipocytes may derive from a progenitor cell distinct from the progenitor for osteoblasts, chondrocytes, and other bone marrow stromal cells  . "
ABSTRACT: Multiple myeloma is a B-cell malignancy characterized by the unrelenting proliferation of plasma cells. Multiple myeloma causes osteolytic lesions and fractures that do not heal due to decreased osteoblastic and increased osteoclastic activity. However, the exact relationship between osteoblasts and myeloma cells remains elusive. Understanding the interactions between these dynamic bone-forming cells and myeloma cells is crucial to understanding how osteolytic lesions form and persist, and how tumors grow within the bone marrow. This review provides a comprehensive overview of basic and translational research focused on the role of osteoblasts in multiple myeloma progression and their relationship to osteolytic lesions. Importantly, current challenges for in vitro studies exploring direct osteoblastic effects on myeloma cells, and gaps in understanding the role of the osteoblast in myeloma progression are delineated. Finally, successes and challenges in myeloma treatment with osteoanabolic therapy (i.e. any treatment that induces increased osteoblastic number or activity) are enumerated. Our goal is to illuminate novel mechanisms by which osteoblasts may contribute to multiple myeloma disease progression and osteolysis to better direct research efforts. Ultimately, we hope this may provide a roadmap for new approaches to the pathogenesis and treatment of multiple myeloma with a particular focus on the osteoblast. Copyright © 2015. Published by Elsevier Inc.
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ABSTRACT: The transdifferentiation of bone and fat is a new insight in studying the increasingly bone marrow fat in the process of osteoporosis of elderly or menopause crowd which is increasing in prevalence. The loss of bone mass in osteoporosis is multifactorially determined and includes genetic, hormonal and environmental determinants. Although it has long been considered whether the transdifferentiation process does exist in vivo and whether it could be find in the same individual, interaction between skeleton and adipose tissue has been proved pre-clinically and clinically by increasing evidence. Here we focus on the current understanding of the transdifferentiation between bone and fat, the molecular interactions and future clinical implications of recent studies linking the transdifferentiation to bone metabolism diseases. Furthermore, a set of recommendations of bone and fat transdifferentiation on bone metabolism are also presented to facilitate evaluation of this magic process.
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ABSTRACT: Age-related bone loss is in large part the consequence of senescence mechanisms that impact bone cell number and function. In recent years, progress has been made in the understanding of the molecular mechanisms underlying bone cell senescence that contributes to the alteration of skeletal integrity during aging. These mechanisms can be classified as intrinsic senescence processes, alterations in endogenous anabolic factors and changes in local support. Intrinsic senescence mechanisms cause cellular dysfunctions that are not tissue specific and include telomere shortening, accumulation of oxidative damage, impaired DNA repair and altered epigenetic mechanisms regulating gene transcription. Aging mechanisms that are more relevant to the bone microenvironment include alterations in the expression and signalling of local growth factors, and altered intercellular communications. This review provides an integrated overview of the current concepts and interacting mechanisms underlying bone cell senescence during aging, and how they could be targeted to reduce the negative impact of senescence in the aging skeleton. © 2014 American Society for Bone and Mineral Research.
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