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

Singh, Lakshman; Tyagi, Sonia; Myers, Damian E.; Duque, Gustavo

doi:10.1007/s11914-018-0427-y

Cited by 57 publications

(50 citation statements)

References 84 publications

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“…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]. The present study showed that knee loading reduced body weight, fat, BMI, the number, perimeter, and area ratio of adipocytes, while it elevated BMD, BMC, the circumference of trabecular bone, and the osteoblast number on the trabecular bone surface.…”

Section: Discussionmentioning

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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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%

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

Liu

et al. 2020

Preprint

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“…Bone marrow adiposity is believed to cause high levels of fatty acids within the bone marrow milieu, which has toxic effects on osteoblasts and osteocytes [121]. A series of in vitro studies demonstrated detrimental effects of palmitic acid on bone cells [122••, 123].…”

Section: Lipids and Fatty Acidsmentioning

confidence: 99%

Marrow Fat-Secreted Factors as Biomarkers for Osteoporosis

Herrmann

2019

Curr Osteoporos Rep

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Purpose of Review The age-related accumulation of bone marrow adipose tissue (BMAT) negatively impacts bone metabolism and hematopoiesis. This review provides an overview about BMAT-secreted factors as biomarkers for BMAT accumulation and osteoporosis risk. Recent Findings The adipokines leptin and adiponectin are regulators of BMAT. It remains to be clarified if locally produced adipokines substantially contribute to their peripheral serum levels and if they influence bone metabolism beyond that of extraosseous adipokine production. Existing data also suggests that BMAT disturbs bone metabolism primarily through palmitate-mediated toxic effects on osteoblasts and osteocytes, including dysregulated autophagy and apoptosis. Summary BMAT-secreted factors are important modulators of bone metabolism. However, the majority of our understanding about MAT-secreted factors and their paracrine and endocrine effects is derived from in vitro studies and animal experiments. Therefore, more research is needed before BMAT-secreted biomarkers can be applied in medical practice. Keywords Bone marrow fat. Adipocytes. Leptin. Adiponectin. Fatty acids This article is part of the Topical Collection on Bone Marrow and Adipose Tissue

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“…This predominant differentiation of MSCs into osteoblasts changes with age, shifting their differentiation into adipocytes. Accumulation of marrow fat plays a toxic role affecting osteoblasts as well as hematopoietic cells, exerted through the secretion of fatty acids and adipokines that accumulate in the bone marrow of aging and osteoporotic bone decreasing osteoblast differentiation, function, and survival while also stimulating osteoclastic activity (Figure ) …”

Section: Pathophysiologymentioning

confidence: 99%

“…Accumulation of marrow fat plays a toxic role affecting osteoblasts as well as hematopoietic cells, exerted through the secretion of fatty acids and adipokines that accumulate in the bone marrow of aging and osteoporotic bone decreasing osteoblast differentiation, function, and survival while also stimulating osteoclastic activity (Figure 1). 14 The pathophysiology of osteosarcopenia involves a combination of fat, muscle, and bone-related mechanisms ( Figure 2). Fat infiltration, and its associated lipotoxic effect, is observed in both muscle and bone independent of body mass index.…”

Section: Pathophysiologymentioning

confidence: 99%

Osteoporosis in Older Persons: Old and New Players

Zanker

Duque

2018

J American Geriatrics Society

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Osteoporosis is the most common bone disease in humans. Older persons are at higher risk of osteoporotic fractures that also result in poor quality of life, disability, loss of independence, institutionalization, and higher mortality. Osteoporosis shares a distinct pathophysiologic relationship with sarcopenia, an age‐related disease comprising declines in muscle mass, strength, or function. The combination of these two diseases is known as osteosarcopenia. Understanding the pathophysiology of osteosarcopenia, in addition to its diagnostic and therapeutic approaches, is key in providing older adults with the best falls and fractures prevention strategies. This review provides updated information on new discoveries on the combined pathophysiology of osteoporosis and sarcopenia that have led to the development of novel therapeutic approaches. New recommendations for the use of risk calculators and densitometry are also presented in this review as well as evidence on current and upcoming pharmacologic treatments to prevent falls and fractures in older persons. J Am Geriatr Soc 67:831–840, 2019.

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

Cited by 57 publications

References 84 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

Marrow Fat-Secreted Factors as Biomarkers for Osteoporosis

Osteoporosis in Older Persons: Old and New Players

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