Pathophysiological role of enhanced bone marrow adipogenesis in diabetic complications

Piccinin, Meghan A.; Khan, Zia A.

doi:10.4161/adip.32215

Cited by 31 publications

(24 citation statements)

References 172 publications

(197 reference statements)

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“…As such, factors that influence MSC lineage allocation can have a profound influence on the balance of cell types present within bone and thus skeletal homeostasis. It is well known that bone marrow adipose tissue increases with age and that reduced bone quantity and quality (i.e., osteopenia or osteoporosis) related to aging [19], menopause [20], diabetes [21, 22], chronic glucocorticoid exposure [23, 24], and anorexia nervosa [25] is frequently associated with elevated bone marrow adipocytes. This indicates at the very least that changes in the physiological milieu that coincides with these states result in greater relative predisposition for MSC adipogenesis versus osteoblastogenesis.…”

Section: Cell-intrinsic Suppression Of Osteoblastogenesismentioning

confidence: 99%

Bone Marrow Adipose Tissue and Skeletal Health

Muruganandan

Govindarajan

Sinal

2018

Curr Osteoporos Rep

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Purpose of Review To summarize and discuss recent progress and novel signaling mechanisms relevant to bone marrow adipocyte formation and its physiological/pathophysiological implications for bone remodeling. Recent Findings Skeletal remodeling is a coordinated process entailing removal of old bone and formation of new bone. Several bone loss disorders such as osteoporosis are commonly associated with increased bone marrow adipose tissue. Experimental and clinical evidence supports that a reduction in osteoblastogenesis from mesenchymal stem cells at the expense of adipogenesis, as well as the deleterious effects of adipocyte-derived signaling, contributes to the etiology of osteoporosis as well as bone loss associated with aging, diabetes mellitus, post-menopause, and chronic drug therapy. However, this view is challenged by findings indicating that, in some contexts, bone marrow adipose tissue may have a beneficial impact on skeletal health. Summary Further research is needed to better define the role of marrow adipocytes in bone physiology/pathophysiology and to determine the therapeutic potential of manipulating mesenchymal stem cell differentiation.

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Section: Cell-intrinsic Suppression Of Osteoblastogenesismentioning

confidence: 99%

Bone Marrow Adipose Tissue and Skeletal Health

Muruganandan

Govindarajan

Sinal

2018

Curr Osteoporos Rep

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“…Together with excess vascular permeability of the diabetic BM microvasculature , these features closely resemble pathological changes typically ongoing in the diabetic retina. Other typical characteristics of BM pathology in murine models and human diabetes include fatty infiltration . As BM adipocytes regulate the stem cell niche , this apparently passive filling may turn out to be a critical element affecting BM function in metabolic diseases.…”

Section: Diabetes the Bone Marrow And Circulating Stem/progenitor Cmentioning

confidence: 99%

Concise Review: Perspectives and Clinical Implications of Bone Marrow and Circulating Stem Cell Defects in Diabetes

2016

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Diabetes mellitus is a complex systemic disease characterized by severe morbidity and excess mortality. The burden of its multiorgan complications relies on an imbalance between hyperglycemic cell damage and defective endogenous reparative mechanisms. Inflammation and abnormalities in several hematopoietic components are typically found in diabetes. The discovery that diabetes reduces circulating stem/progenitor cells and impairs their function has opened an entire new field of study where diabetology comes into contact with hematology and regenerative medicine. It is being progressively recognized that such rare circulating cell populations mirror finely regulated processes involved in hematopoiesis, immunosurveillance, and peripheral tissue homeostasis. From a clinical perspective, pauperization of circulating stem cells predicts adverse outcomes and death. Furthermore, studies in murine models and humans have identified the bone marrow (BM) as a previously neglected site of diabetic end-organ damage, characterized by microangiopathy, neuropathy, fat deposition, and inflammation. As a result, diabetes impairs the mobilization of BM stem/ progenitor cells, a defect known as mobilopathy or myelokathexis, with negative consequences for physiologic hematopoiesis, immune regulation, and tissue regeneration. A better understanding of the molecular and cellular processes that govern the BM stem cell niche, cell mobilization, and kinetics in peripheral tissues may uncover new therapeutic strategies for patients with diabetes. This concise review summarizes the current knowledge on the interplay between the BM, circulating stem cells, and diabetes, and sets the stages for future developments in the field. STEM CELLS 2017;35:106-116 SIGNIFICANCE STATEMENTDiabetes leads to multiorgan complications that reduce life expectancy. Organ damage in diabetes results from glucose toxicity, defective tissue repair, inflammation, and disturbances in several hematopoietic components. Importantly, diabetes reduces circulating stem/progenitor cells involved in hematopoiesis, immunosurveillance, and peripheral tissue homeostasis. This alteration is attributable to microangiopathy, neuropathy, fat deposition, and inflammation in the bone marrow, which emerges as a previously neglected site of diabetic end-organ damage. As a result, diabetes impairs the mobilization and availability of stem/progenitor cells, which in turn predicts adverse outcomes and death.

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“…Activation of mechanistic target of rapamycin (mTOR) increases adipocyte specific factors in preadipocytes and increases muscle satellite cells [ 33 ]. The PI3K/PKB pathway is also stimulated by oxidative stress generated by ROS and enhances adipogenesis, thereby decreasing osteoclastogenesis [ 55 ].…”

Section: Resultsmentioning

confidence: 99%

Molecular Modulation of Osteoblasts and Osteoclasts in Type 2 Diabetes

Rathinavelu

Guidry-Elizondo

Banu

2018

Journal of Diabetes Research

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Diabetes is a common disease affecting majority of populations worldwide. Since 1980, there has been an increase in the number of people diagnosed as prediabetic and diabetic. Diabetes is characterized by high levels of circulating glucose and leads to most microvascular and macrovascular complications such as retinopathy, nephropathy, neuropathy, stroke, and myocardial infarction. Bone marrow vascular disruption and increased adiposity are also linked to various complications in type II diabetes mellitus. In addition to these complications, type 2 diabetic patients also have fragile bones caused by faulty mineralization mainly due to increased adiposity among diabetic patients that affects both osteoblast and osteoclast functions. Other factors that increase fracture risk in diabetic patients are increased oxidative stress, inflammation, and drugs administered to diabetic patients. This review reports the modulation of different pathways that affect bone metabolism in diabetic conditions.

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Pathophysiological role of enhanced bone marrow adipogenesis in diabetic complications

Cited by 31 publications

References 172 publications

Bone Marrow Adipose Tissue and Skeletal Health

Bone Marrow Adipose Tissue and Skeletal Health

Concise Review: Perspectives and Clinical Implications of Bone Marrow and Circulating Stem Cell Defects in Diabetes

Molecular Modulation of Osteoblasts and Osteoclasts in Type 2 Diabetes

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