The Implications of Bone Marrow Adipose Tissue on Inflammaging

Aaron, Nicole; Costa, Samantha; Rosen, Clifford J.; Li, Qiang

doi:10.3389/fendo.2022.853765

Cited by 33 publications

(31 citation statements)

References 132 publications

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“…Our studies further suggest that the trabecular osteoblast's need for fatty acids is supported by PTH signaling in adipocytes. Bone-adipose interactions have been studied in several contexts as a result of the increase in bone marrow adiposity as bone mass decreases during the aging process (35,36) and the negative association between body mass index and bone mass (37)(38)(39). On the one hand, adipocytes produce adipokines, such as leptin and adiponectin, that suppress osteoblast function and lead to bone loss (40)(41)(42).…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial β-oxidation of adipose-derived fatty acids by osteoblasts fuels parathyroid hormone–induced bone formation

Alekos¹,

Kushwaha²,

Kim³

et al. 2023

JCI Insight

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The energetic costs of bone formation require osteoblasts to coordinate their activities with tissues, like adipose, that can supply energy-dense macronutrients. In the case of intermittent parathyroid hormone treatment (PTH), a strategy used to reduce fracture risk, bone formation is proceeded by a change in systemic lipid homeostasis. To investigate the requirement for fatty acid oxidation by osteoblasts during PTH-induced bone formation, we subjected mice with osteoblast-specific deficiency of mitochondrial longchain b-oxidation as well as mice with adipocyte-specific deficiency for the PTH receptor or adipose triglyceride lipase to an anabolic treatment regime. PTH increased the release of fatty acids from adipocytes and b-oxidation by osteoblasts, while the genetic mouse models were resistant to the hormone's anabolic effect. Collectively, these data suggest that PTH's anabolic actions requires coordinated signaling between bone and adipose, wherein a lipolytic response liberates fatty acids that are oxidized by osteoblasts to fuel bone formation

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Section: Discussionmentioning

confidence: 99%

Mitochondrial β-oxidation of adipose-derived fatty acids by osteoblasts fuels parathyroid hormone–induced bone formation

Alekos¹,

Kushwaha²,

Kim³

et al. 2023

JCI Insight

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“…BMAds are important contributors to systemic adipokine levels ( 12 ), as well as regulators of bone ( 13 ) via RANKL expression ( 14 ) and hematopoiesis via stem cell factor (SCF) production ( 15 ), and have recently been implicated in bone metastatic cancers such as acute myeloid leukemia ( 16 ) and breast cancer ( 17 ). Interestingly, BM adipose tissue (BMAT) expands with aging and obesity ( 18 , 19 ), which are the two key risk factors for MM ( 20 – 22 ), suggesting that BMAds interact with and influence myeloma cells in the marrow. Indeed, adipocyte-derived factors such as monocyte chemoattractant protein 1 (MCP-1) and stromal cell-derived factor 1 (SDF1) are known chemotactic factors for myeloma cells ( 9 , 23 ), whereas other factors promote myeloma proliferation (e.g., leptin) ( 10 ) and resistance to chemotherapies (e.g., leptin and adipsin) ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

Development and characterization of three cell culture systems to investigate the relationship between primary bone marrow adipocytes and myeloma cells

et al. 2023

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The unique properties of the bone marrow (BM) allow for migration and proliferation of multiple myeloma (MM) cells while also providing the perfect environment for development of quiescent, drug-resistant MM cell clones. BM adipocytes (BMAds) have recently been identified as important contributors to systemic adipokine levels, bone strength, hematopoiesis, and progression of metastatic and primary BM cancers, such as MM. Recent studies in myeloma suggest that BMAds can be reprogrammed by tumor cells to contribute to myeloma-induced bone disease, and, reciprocally, BMAds support MM cells in vitro. Importantly, most data investigating BMAds have been generated using adipocytes generated by differentiating BM-derived mesenchymal stromal cells (BMSCs) into adipocytes in vitro using adipogenic media, due to the extreme technical challenges associated with isolating and culturing primary adipocytes. However, if studies could be performed with primary adipocytes, then they likely will recapitulate in vivo biology better than BMSC-derived adipocytes, as the differentiation process is artificial and differs from in vivo differentiation, and progenitor cell(s) of the primary BMAd (pBMAds) may not be the same as the BMSCs precursors used for adipogenic differentiation in vitro. Therefore, we developed and refined three methods for culturing pBMAds: two-dimensional (2D) coverslips, 2D transwells, and three-dimensional (3D) silk scaffolds, all of which can be cultured alone or with MM cells to investigate bidirectional tumor-host signaling. To develop an in vitro model with a tissue-like structure to mimic the BM microenvironment, we developed the first 3D, tissue engineered model utilizing pBMAds derived from human BM. We found that pBMAds, which are extremely fragile, can be isolated and stably cultured in 2D for 10 days and in 3D for up to 4 week in vitro. To investigate the relationship between pBMAds and myeloma, MM cells can be added to investigate physical relationships through confocal imaging and soluble signaling molecules via mass spectrometry. In summary, we developed three in vitro cell culture systems to study pBMAds and myeloma cells, which could be adapted to investigate many diseases and biological processes involving the BM, including other bone-homing tumor types.

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“…Similarly, BMSCs obtained from obese men exhibited enhanced adipocyte differentiation and accelerated senescence phenotype that would contribute to the skeletal fragility in obesity ( 71 ). T2D is another risk factor in skeletal fragility and osteoporosis in aging men and postmenopausal women ( 128 – 130 ), despite the increase in BMD or independent of BMD ( 131 , 132 ). The combination of obesity and T2D were shown to exhibit higher serum insulin levels and BMA at the lumbar spine and femoral metaphysis compared to the subjects without T2D.…”

Section: Obesity and Diabetesmentioning

confidence: 99%

The pathophysiology of osteoporosis in obesity and type 2 diabetes in aging women and men: The mechanisms and roles of increased bone marrow adiposity

Ali

Tencerová²,

Figeac³

et al. 2022

Front. Endocrinol.

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Osteoporosis is defined as a systemic skeletal disease characterized by decreased bone mass and micro-architectural deterioration leading to increased fracture risk. Osteoporosis incidence increases with age in both post-menopausal women and aging men. Among other important contributing factors to bone fragility observed in osteoporosis, that also affect the elderly population, are metabolic disturbances observed in obesity and Type 2 Diabetes (T2D). These metabolic complications are associated with impaired bone homeostasis and a higher fracture risk. Expansion of the Bone Marrow Adipose Tissue (BMAT), at the expense of decreased bone formation, is thought to be one of the key pathogenic mechanisms underlying osteoporosis and bone fragility in obesity and T2D. Our review provides a summary of mechanisms behind increased Bone Marrow Adiposity (BMA) during aging and highlights the pre-clinical and clinical studies connecting obesity and T2D, to BMA and bone fragility in aging osteoporotic women and men.

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The Implications of Bone Marrow Adipose Tissue on Inflammaging

Cited by 33 publications

References 132 publications

Mitochondrial β-oxidation of adipose-derived fatty acids by osteoblasts fuels parathyroid hormone–induced bone formation

Mitochondrial β-oxidation of adipose-derived fatty acids by osteoblasts fuels parathyroid hormone–induced bone formation

Development and characterization of three cell culture systems to investigate the relationship between primary bone marrow adipocytes and myeloma cells

The pathophysiology of osteoporosis in obesity and type 2 diabetes in aging women and men: The mechanisms and roles of increased bone marrow adiposity

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