The Role of Bone Marrow Microenvironment in Governing the Balance between Osteoblastogenesis and Adipogenesis

Li, Jiao; Liu, Xingyu; Zuo, Bin; Zhang, Li

doi:10.14336/ad.2015.1206

Cited by 80 publications

(61 citation statements)

References 124 publications

(128 reference statements)

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“…Increasing levels of marrow fat would affect bone metabolism through a variety of mechanisms. This has been demonstrated by studies showing that osteoporosis can be introduced in normal mice by injection of total bone marrow cells from old mice directly into the bone marrow cavity of normal recipients [36][37][38][39]. However, the specific mechanisms involved in this lipotoxic effect have been partially explored.…”

Section: Mechanisms and Consequences Of Lipotoxicity In Bonementioning

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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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: Mechanisms and Consequences Of Lipotoxicity In Bonementioning

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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“…Elevated bone marrow adiposity (BMA) is observed when mesenchymal stem cells (MSCs) preferentially differentiate into adipocytes, causing fat deposits to accumulate in the bone marrow. BMA is also shown to increase with age as demonstrated by a greater distribution of adipose tissue versus bone cells within bone . Justesen and colleagues reported a larger proportion of adipocytes in postmortem iliac crest bone biopsies from age 30 (40%) toward age 100 (68%) .…”

Section: Introductionmentioning

confidence: 99%

“…BMA is also shown to increase with age as demonstrated by a greater distribution of adipose tissue versus bone cells within bone. (2,3) Justesen and colleagues reported a larger proportion of adipocytes in postmortem iliac crest bone biopsies from age 30 (40%) toward age 100 (68%). (4) This disproportion of bone versus fat can compromise overall bone strength, translating to an increase in osteoporotic fractures.…”

Section: Introductionmentioning

confidence: 99%

Bone Marrow and Muscle Fat Infiltration Are Correlated among Postmenopausal Women With Osteoporosis: The AMBERS Cohort Study

Wong

Chandrakumar

Whyte

et al. 2019

Journal of Bone and Mineral Research

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Bone and muscle have shown to interact, but little is known about fat within bone and muscle. Clinical studies have isolated fat within bone and muscle using MRI. In this cross‐sectional study, we hypothesized that bone marrow adiposity and muscle adiposity are related and that this relationship is associated with osteoporosis. Postmenopausal women aged 60 to 85 years were recruited as part of the Appendicular Muscle and Bone Extension Research Study (AMBERS). Participants completed dual‐energy X‐ray absorptiometry (DXA) of the hip and spine to diagnose osteoporosis. Muscle adiposity was measured with MRI at the 66% site of the leg. Fat segmentation was achieved using a semi‐automated iterative threshold‐optimizing algorithm (error < 5%). Peripheral quantitative computed tomography measured marrow density of the 4% distal tibia (surrogate for marrow fat) by threshold‐based, edge‐detection segmentations and by examining residuals from trabecular bone density regressed on trabecular tissue mineral density. Muscle adiposity from MRI was regressed on marrow density using linear regression. Models were further examined with an interaction with osteoporosis status. Among 312 women (aged 75.4 ± 5.9 years, body mass index [BMI] 29.5 ± 5.7 kg/m2), a larger amount of muscle fat was associated with lower marrow density at the 66% mid‐tibia (B = 84.08 [27.56], p = 0.002) and at the 4% distal tibia (B = 129.17 [55.96], p = 0.022) after accounting for age, height, weight, average daily energy expenditure, hypertension, and diabetes. Interactions of this relationship with osteoporosis status were also significant. Upon probing these interactions, the relationships were significant only in women with osteoporosis but not in those without osteoporosis. Fat from bone marrow and muscle may be related to one another through the same phenomenon, which is likely also responsible for osteoporosis, but independent of hypertension and diabetes. More research should focus on the potential abnormalities in muscle and bone fat metabolism and mesenchymal cell commitment to fat within patients with osteoporosis. © 2019 American Society for Bone and Mineral Research.

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“…As BMSCs undergo differentiation, changes occur in their transcriptional profile, cellular metabolism, and morphology that are consistent with the respective lineage of commitment. During aging and in pathological conditions, the normal balance between osteogenic and adipogenic cell populations can shift toward the latter, thereby threatening bone health and integrity (2). Here we review the osteoblast-adipocyte relationship within the bone marrow and provide insights into how these two cell types can be better defined.…”

Section: Introductionmentioning

confidence: 99%

Defining osteoblast and adipocyte lineages in the bone marrow

Pierce

Begun

Westendorf

et al. 2019

Bone

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Bone is a complex endocrine organ that facilitates structural support, protection to vital organs, sites for hematopoiesis, and calcium homeostasis. The bone marrow microenvironment is a heterogeneous niche consisting of multipotent musculoskeletal and hematopoietic progenitors and their derivative terminal cell types. Amongst these progenitors, bone marrow mesenchymal stem/stromal cells (BMSCs) may differentiate into osteogenic, adipogenic, myogenic, and chondrogenic lineages to support musculoskeletal development as well as tissue homeostasis, regeneration and repair during adulthood. With age, the commitment of BMSCs to osteogenesis slows, bone formation decreases, fracture risk rises, and marrow adiposity increases. An unresolved question is whether osteogenesis and adipogenesis are co-regulated in the bone marrow. Osteogenesis and adipogenesis are controlled by specific signaling mechanisms, circulating cytokines, and transcription factors such as Runx2 and Pparγ, respectively. One hypothesis is that adipogenesis is the default pathway if osteogenic stimuli are absent. However, recent work revealed that Runx2 and Osx1-expressing preosteoblasts form lipid droplets under pathological and aging conditions. Histone deacetylase 3 (Hdac3) and other epigenetic regulators suppress lipid storage in preosteoblasts and/or control marrow adiposity. Establishing a better understanding of fat storage in bone marrow cells, as well as the osteoblast-adipocyte relationship within the bone marrow niche is necessary to understand the mechanisms underlying disease- and aging-related marrow fat storage and may lead to the development of new therapeutic targets for "fatty bone" and osteoporosis.

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The Role of Bone Marrow Microenvironment in Governing the Balance between Osteoblastogenesis and Adipogenesis

Cited by 80 publications

References 124 publications

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

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

Bone Marrow and Muscle Fat Infiltration Are Correlated among Postmenopausal Women With Osteoporosis: The AMBERS Cohort Study

Defining osteoblast and adipocyte lineages in the bone marrow

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