Evolution of the Marrow Adipose Tissue Microenvironment

Craft, Clarissa S.; Scheller, Erica L.

doi:10.1007/s00223-016-0168-9

Cited by 26 publications

(20 citation statements)

References 132 publications

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“…The bone marrow microenvironment is a very active milieu, which involves multiple interactions between cells, hormones, growth factors, neural connections, and the vasculature [1][2][3]. These interactions are affected by the normal aging process and in higher proportion by diseases such as osteoporosis.…”

Section: Introductionmentioning

confidence: 99%

“…There is still controversy whether high volumes of marrow fat play a negative, positive or neutral role in the bone marrow [2,[7][8][9], which would depend on the physiological or pathological role of marrow fat and its secreted factors. Indeed, the understanding of the biological role of marrow adipocytes has gone from just replacing the vacuum left by other bone tissues, to having very active thermogenic and metabolic roles [10,11].…”

Section: Introductionmentioning

confidence: 99%

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Good, Bad, or Ugly: the Biological Roles of Bone Marrow Fat

Singh

Tyagi

Myers

et al. 2018

Curr Osteoporos Rep

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Lipotoxicity in the bone is exerted by bone marrow fat through the secretion of adipokines and free fatty acids (FFA) (predominantly palmitate). High levels of FFA found in the bone marrow of aged and osteoporotic bone are associated with decreased osteoblastogenesis and bone formation, decreased hematopoiesis, and increased osteoclastogenesis. In addition, FFA such as palmitate and stearate induce apoptosis and dysfunctional autophagy in the osteoblasts, thus affecting their differentiation and function. Regulation of marrow fat could become a therapeutic target for osteoporosis. Inhibition of the synthesis of FFA by marrow fat could facilitate osteoblastogenesis and bone formation while affecting osteoclastogenesis. However, further studies testing this hypothesis are still required.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Good, Bad, or Ugly: the Biological Roles of Bone Marrow Fat

Singh

Tyagi

Myers

et al. 2018

Curr Osteoporos Rep

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“…Overall, healthy obesity is not necessarily detrimental for the skeleton, as increased mechanical loading on weight-bearing bones usually improves BMD, making the bones less susceptible to fractures [ 21 , 22 ]. However, aggressive expansion of adipose tissue in the liver and other organs leads to uncontrolled secretion of adipokines that can negatively impact overall metabolism and inflammatory responses throughout the body [ 23 , 24 ]. For example, the shift of differentiation of mesenchymal stem cells toward adipocytes and accumulation of adipocytes in the bone marrow negatively impact bone metabolism [ 25 – 27 ].…”

Section: Discussionmentioning

confidence: 99%

Metabolic Syndrome and Bone: Pharmacologically Induced Diabetes has Deleterious Effect on Bone in Growing Obese Rats

2017

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Metabolic syndrome and osteoporosis share similar risk factors. Also, patients with diabetes have a higher risk of osteoporosis and fracture. Liver manifestations, such as non-alcoholic steatohepatitis (NASH), of metabolic syndrome are further aggravated in diabetics and often lead to liver failure. Our objective was to create a rat model of human metabolic syndrome and determine the long-term impact of early-onset T1D on bone structure and strength in obese growing rats. Male rats were given either standard chow and RO water (Controls) or a high-fat, high-cholesterol diet and sugar water containing 55% fructose and 45% glucose (HFD). A third group of rats received the HFD diet and a single dose of streptozotocin to induce type 1 diabetes (HFD/Sz). Body weight and glucose tolerance tests were conducted several times during the course of the study. Serum chemistry, liver enzymes, and biomarkers of bone metabolism were evaluated at 10 and 28 weeks. Shear wave elastography and histology were used to assess liver fibrosis. Cancellous bone structure and cortical bone geometry were evaluated by mCT and strength by the 3-point bending method. Body mass and fat accumulation was significantly higher in HFD and HFD/Sz rats compared to Controls. Rats in both the HFD and HFD/Sz groups developed NASH, although the change was more severe in diabetic rats. Although both groups of obese rats had larger bones, their cancellous structure and cortical thickness were reduced, resulting in diminished strength that was further aggravated by diabetes. The HFD and HFD/Sz rats recapitulate MeSy in humans with liver pathology consistent with NASH. Our data provide strong indication that obesity accompanied by type 1 diabetes significantly aggravates comorbidities of MeSy, including the development of osteopenia and weaker bones. The juvenile rat skeleton seems to be more vulnerable to damage imposed by obesity and diabetes and may offer a model to inform the underlying pathology associated with the unusually high fracture rates in obese adults with diabetes.

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“…Figure 1 summarizes this model. For additional perspectives on MAT, we direct the reader to recent reviews [9–13], including ones focusing on the relationship between MAT and energy metabolism [14], MAT and energy deficit [15], MAT and fatty infiltration of skeletal muscle [16], MAT and diabetes [17], MAT and exercise [18], and MAT and cancer metastasis [19, 20].…”

Section: Introductionmentioning

confidence: 99%

Metabolic Coupling Between Bone Marrow Adipose Tissue and Hematopoiesis

Turner

Martin

Iwaniec

2018

Curr Osteoporos Rep

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An important physiological function of MAT may be to provide an expandable/contractible fat depot, which is critical for minimization of energy requirements for sustaining optimal hematopoiesis. Because the energy requirements for storing fat are negligible compared to those required to maintain hematopoiesis, even small reductions in hematopoietic tissue volume to match a reduced requirement for hematopoiesis could represent an important reduction in energy cost. Such a physiological function would require tight coupling between hematopoietic stem cells and MSCs to regulate the balance between MAT and hematopoiesis. Kit-ligand, an important regulator of proliferation, differentiation, and survival of hematopoietic cells, may function as a prototypic factor coupling MAT and hematopoiesis. Crosstalk between hematopoietic and mesenchymal cells in the bone marrow may contribute to establishing the balance between MAT levels and hematopoiesis.

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Evolution of the Marrow Adipose Tissue Microenvironment

Cited by 26 publications

References 132 publications

Good, Bad, or Ugly: the Biological Roles of Bone Marrow Fat

Good, Bad, or Ugly: the Biological Roles of Bone Marrow Fat

Metabolic Syndrome and Bone: Pharmacologically Induced Diabetes has Deleterious Effect on Bone in Growing Obese Rats

Metabolic Coupling Between Bone Marrow Adipose Tissue and Hematopoiesis

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