Bone Marrow Adiposity: Basic and Clinical Implications

Sebo, Zachary L; Rendina-Ruedy, Elizabeth; Ables, Gene P.; Lindskog, Dieter M.; Rodeheffer, Matthew S.; Fazeli, Pouneh K.; Horowitz, Mark C.

doi:10.1210/er.2018-00138

Cited by 81 publications

(73 citation statements)

References 181 publications

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“…Understanding the effect of the marrow fat on bone metabolism is pivotal. Due to the accumulation of marrow adipose tissue [4], osteoporosis caused by obesity is characterized by an increase in marrow fat and a decrease in BMD in trabecular bone [41]. Regulating marrow adipocytes may be considered as a potential therapeutic target for osteoporosis [42].…”

Section: Discussionmentioning

confidence: 99%

“…The bone marrow represents an important compartment to regulate mineral homeostasis [3]. Adipose tissue in the bone marrow (marrow adipose tissue; MAT) plays a critical role in obesity [4]. Adipocytes are generated from mesenchymal stem cells (MSCs) in bone marrow milieu, and are derived from the same stem cell lineage as osteoblasts [5,6].…”

Section: Introductionmentioning

confidence: 99%

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Mechanical Loading Prevents Obesity-Associated Bone Loss by Maintaining the Balance between Adipocytes and Osteoblasts

Liu

et al. 2020

Preprint

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Background: Globally increasing obesity is closely linked to bone homeostasis. Maintaining the balance between differentiate of adipocytes and osteoblasts from bone marrow mesenchymal stem cells (BMSCs) is important for bone homeostasis. While mechanical loading has been shown to improve bone remodeling by promoting osteoblast differentiation, little is known about its effects on obesity-associated bone loss. Methods: Using obese mice induced by high-fat diet and ovariectomy (OVX), the effects of mechanical loading in a form of knee loading (1 N, 5 Hz, 6 min/day) was applied with for 4 weeks. The mice were sorted into five groups: standard diet control (SC), high-fat diet control (HF), HF and loading (HFL), HF and ovariectomy (HO), and HO and loading (HOL). Femurs were harvested for histomorphometry analysis. Bone marrow-derived cells were isolated to examine the banlance between differentiation of adipocytes and osteoblasts. Immunohistochemical analyses and Western blotting analyses were performed to evaluate markers for adipocytes, osteoblasts, and Wnt signaling.Results: High-fat diet presented higher body weight, body fat, and body mass index (BMI), as well as bone loss than standard diet, and the detrimental changes in OVX mice were even higher. The daily application of knee loading significantly decreased BMI, the numbers and perimeter of adipocytes, and the differentiation of adipocytes. The expression of C/EBPα and PPARγ were suppressed by knee loading. The loaded group also presented a significant increase in bone mineral density and contents, and the circumference of trabecular bone. Regarding osteoblasts, knee loading enhanced the number of osteoblasts on bone surface, differentiation of osteoblasts, and the level of Runx2 and ALP. Furthermore, Wnt signaling involved in the effect of knee loading on attenuating obesity-induced bone loss. Conclusions: This study supported evidence that knee loading offers a new therapeutic option to prevent obesity-related bone loss by altering the balance between adipocytes and osteoblasts in the bone marrow, and the effect is associated with Wnt signaling.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mechanical Loading Prevents Obesity-Associated Bone Loss by Maintaining the Balance between Adipocytes and Osteoblasts

Liu

et al. 2020

Preprint

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“…Through these factors BMAds are reported to modulate haematopoiesis and skeletal remodelling. A full discussion of these functions is beyond the scope of this position paper, but more details are available in several recent reviews (80,99,100). Relating to lipid storage, an unresolved question concerns BM adipocytes' unilocular vs. multilocular nature.…”

Section: Bone Marrow Adipocytesmentioning

confidence: 99%

Standardised Nomenclature, Abbreviations, and Units for the Study of Bone Marrow Adiposity: Report of the Nomenclature Working Group of the International Bone Marrow Adiposity Society

et al. 2020

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“…This classification is based on their appearance, function, and site of origin ( 12 ). Although BMAs possess some characteristics of white adipocytes, they appear to be a distinct fourth population of adipocytes, a previously unrecognized fat depot ( 13 ). BMA is characterized by a unilocular lipid droplet within a cytoplasm that is surrounded by a lipid membrane and an adjacent single nucleus.…”

Section: Introductionmentioning

confidence: 99%

Bone Marrow Adipocytes, Adipocytokines, and Breast Cancer Cells: Novel Implications in Bone Metastasis of Breast Cancer

Liu

Zhao

2020

Front. Oncol.

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Accumulating discoveries highlight the importance of interaction between marrow stromal cells and cancer cells for bone metastasis. Bone is the most common metastatic site of breast cancer and bone marrow adipocytes (BMAs) are the most abundant component of the bone marrow microenvironment. BMAs are unique in their origin and location, and recently they are found to serve as an endocrine organ that secretes adipokines, cytokines, chemokines, and growth factors. It is reasonable to speculate that BMAs contribute to the modification of bone metastatic microenvironment and affecting metastatic breast cancer cells in the bone marrow. Indeed, BMAs may participate in bone metastasis of breast cancer through regulation of recruitment, invasion, survival, colonization, proliferation, angiogenesis, and immune modulation by their production of various adipocytokines. In this review, we provide an overview of research progress, focusing on adipocytokines secreted by BMAs and their potential roles for bone metastasis of breast cancer, and investigating the mechanisms mediating the interaction between BMAs and metastatic breast cancer cells. Based on current findings, BMAs may function as a pivotal modulator of bone metastasis of breast cancer, therefore targeting BMAs combined with conventional treatment programs might present a promising therapeutic option.

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Bone Marrow Adiposity: Basic and Clinical Implications

Cited by 81 publications

References 181 publications

Mechanical Loading Prevents Obesity-Associated Bone Loss by Maintaining the Balance between Adipocytes and Osteoblasts

Mechanical Loading Prevents Obesity-Associated Bone Loss by Maintaining the Balance between Adipocytes and Osteoblasts

Standardised Nomenclature, Abbreviations, and Units for the Study of Bone Marrow Adiposity: Report of the Nomenclature Working Group of the International Bone Marrow Adiposity Society

Bone Marrow Adipocytes, Adipocytokines, and Breast Cancer Cells: Novel Implications in Bone Metastasis of Breast Cancer

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