Skeletal aging and the adipocyte program

Lecka‐Czernik, Beata; Rosen, Clifford J.; Kawai, Masanobu

doi:10.4161/cc.9.18.13046

Cited by 51 publications

(34 citation statements)

References 74 publications

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“…This is in line with observations from mouse models of aging, where increased adiposity and associated enhancement of PPARγ2 expression, as well as reduced Cbfa1 levels, correlate with decreased bone mass [49, 50]. In addition to changes in MSC fate, aging bone is associated with increases in osteoclast differentiation, process driven by PPARγ and pro-osteoclastic cytokines: macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor κB ligand (RANKL) [43, 44, 51, 52]. Together, these age-related changes in adipo-, osteoblasto-, and osteo-clastogenesis pathways have been linked to low bone mineral density (BMD) and osteoporosis [43, 50].…”

Section: Bone-fat Relationship: Impact Of Marrow Adiposity On Bone mentioning

confidence: 89%

Bone marrow fat: linking adipocyte-induced inflammation with skeletal metastases

Hardaway

Herroon

Rajagurubandara

et al. 2014

Cancer Metastasis Rev

115

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Adipocytes are important but underappreciated components of bone marrow microenvironment, and their numbers greatly increase with age, obesity, and associated metabolic pathologies. Age and obesity are also significant risk factors for development of metastatic prostate cancer. Adipocytes are metabolically active cells that secrete adipokines, growth factors, and inflammatory mediators; influence behavior and function of neighboring cells; and have a potential to disturb local milleu and dysregulate normal bone homeostasis. Increased marrow adiposity has been linked to bone marrow inflammation and osteoporosis of the bone, but its effects on growth and progression of prostate tumors that have metastasized to the skeleton are currently not known. This review focuses on fat-bone relationship in a context of normal bone homeostasis and metastatic tumor growth in bone. We discuss effects of marrow fat cells on bone metabolism, hematopoiesis, and inflammation. Special attention is given to CCL2- and COX-2-driven pathways and their potential as therapeutic targets for bone metastatic disease.

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Section: Bone-fat Relationship: Impact Of Marrow Adiposity On Bone mentioning

confidence: 89%

Bone marrow fat: linking adipocyte-induced inflammation with skeletal metastases

Hardaway

Herroon

Rajagurubandara

et al. 2014

Cancer Metastasis Rev

115

View full text Add to dashboard Cite

show abstract

“…While in certain cases (e.g., obesity and ovariectomy) WAT and BMAT correlate [9], and both can be reduced with exercise [10], no relationship between WAT and MAT was found in type 2 diabetic patients [11]. MAT also increases with age [12,13] and mesenchymal stem cells (MSCs) from older individuals (rodent and human) are more prone to adipogenic differentiation rather than osteogenic or chondrogenic differentiation [14,15]. Therefore, as myeloma also correlates with aging, it is of great interest to determine if this relationship is correlative or also has a causative nature.…”

Section: Bone Marrow Adipocytes Are Distinct From White Adipocytesmentioning

confidence: 99%

Reflections on Cancer in the Bone Marrow: Adverse Roles of Adipocytes

2017

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This review highlights the recent advances in our understanding of adipocyte contributions to carcinogenesis or cancer disease progression for cancers in the bone. Purpose In this review, we aim to describe bone marrow adipose tissue and discuss the soluble adipocyte-derived cytokines (adipokines) or endocrine factors, adipocyte-derived lipids, and the actual or putative juxtacrine signaling between bone marrow adipocytes and tumor cells in the bone marrow. This relationship likely affects tumor cell initiation, proliferation, metastasis, and/or drug resistance. Recent Findings Bone marrow adipose may affect tumor proliferation, drug resistance, or cancer-induced bone disease and hence may be a new target in the fight against cancer. Summary Overall, evidence is mixed regarding the role of bone marrow adipose and adipocytes in cancer progression, and more research in this arena is necessary to determine how these bone marrow microenvironmental cells contribute to malignancies in the marrow to identify novel, potentially targetable pathways.

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“…Consistent with this observation Tavasolli and colleagues found a substantial amount of adipose tissue in adult rabbit BM (Bigelow and Tavassoli, 1984). The accumulation of adipocytes in BM (femur and tibia) appears to be conserved among higher vertebrates, because adipocytes also increase in human and mouse BM with age (Chinn et al, 2012, Justesen et al, 2001, Lecka-Czernik et al, 2010, Rosen et al, 2009, Tuljapurkar et al, 2011). In these cases, the accumulation of adipocytes occurs later in life, coincident with the decline in B lymphopoiesis.…”

Section: Age-related Changes To the Bm Microenvironmentmentioning

confidence: 99%

Bone marrow fat and the decline of B lymphopoiesis in rabbits

Kennedy

Witte

Knight

2016

Developmental & Comparative Immunology

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B lymphopoiesis is necessary to generate a diverse pool of naïve B cells that are able to respond to a broad spectrum of antigens during immune responses to pathogens and to vaccination. Rabbits have been utilized for many years to generate high affinity monoclonal and polyclonal antibodies. Specific antibodies generated in rabbits have greatly advanced scientific discoveries, but the unique qualities of rabbit B cell development have been underappreciated. Unlike in humans and mice, where B lymphopoiesis declines in mid to late life, B lymphopoiesis in rabbits arrests early in life, between 2–4 months of age. This review focuses on the early loss of B cell development in rabbits and the contribution of the bone marrow microenvironment to this process. We also propose directions for future research in this area, and discuss how the rabbit can be used as a model to understand the decline of B lymphopoiesis that occurs in humans late in life. Such studies will be important for developing therapeutics targeted to prevent and/or reverse declining B lymphopoiesis in the elderly, as well as boosting immunity and antibody responses after infection or vaccination.

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Skeletal aging and the adipocyte program

Cited by 51 publications

References 74 publications

Bone marrow fat: linking adipocyte-induced inflammation with skeletal metastases

Bone marrow fat: linking adipocyte-induced inflammation with skeletal metastases

Reflections on Cancer in the Bone Marrow: Adverse Roles of Adipocytes

Bone marrow fat and the decline of B lymphopoiesis in rabbits

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