Osteoclastogenesis by Bone Marrow-Derived Macrophages Is Enhanced in Obese Mice

Kyung, Tae-Wook; Lee, Jieun; Phan, Tien Van; Yu, Rina; Choi, Hye-Seon

doi:10.3945/jn.108.100032

Cited by 51 publications

(43 citation statements)

References 36 publications

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“…Taken together, the results from the model of Halade et al [110,118 ]indicate that with aging increased bone marrow adiposity leads to an upregulation of pro-inflammatory cytokines and consequently to increased bone resorption but decreased bone formation. These findings are in line with those of Kyung et al [119], who described an enhanced osteoclastogenesis in bone marrow-derived macrophages from obese mice. The importance of bone marrow adiposity in the pathophysiology of osteoporosis is further corroborated by studies in humans.…”

Section: Age-related Osteoporosis: An Inflammatory Disease?supporting

confidence: 82%

Advances in Osteoimmunology: Pathophysiologic Concepts and Treatment Opportunities

Rauner

Sipos²,

Thiele³

et al. 2012

Int Arch Allergy Immunol

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Osteoimmunology is an emerging research area that deals with the mutual interactions between bone and the immune system. Osteoclasts have long been the center of attention in osteoimmunological research due to their hematopoietic origin and strong activation through cytokines. However, also the osteoclast’s opponent – the osteoblast – has recently sought the spotlight, and novel functions of its descendant – the osteocyte – have been unraveled. A considerable number of investigations carried out over the past decade have identified critical proteins with osteoimmune functions including the pro-osteoclastic cytokine receptor activator of NF-ĸB ligand and inhibitors of the pro-osteoblastic Wnt signaling pathway. These discoveries have also led to the development of targeted therapies to counteract not only inflammation-induced bone loss but also postmenopausal osteoporosis and osteoporosis associated with aging.

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Section: Age-related Osteoporosis: An Inflammatory Disease?supporting

confidence: 82%

Advances in Osteoimmunology: Pathophysiologic Concepts and Treatment Opportunities

Rauner

Sipos²,

Thiele³

et al. 2012

Int Arch Allergy Immunol

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“…Several mechanisms have been proposed to explain HFD-induced osteoclastogenesis, including elevated levels of in the blood of the pro-inflammatory cytokines IL-1 and TNF derived from adipose tissue macrophages [37], increased RANKL expression from bones [7, 9], and decreased expression of the anti-osteoclastogenic cytokine IL-10 [38]. Interestingly, we found a considerable increase in osteoclast formation from M-CSF-dependent myeloid precursors from bone marrow, but not from spleen cells of HFD-fed mice.…”

Section: Discussionmentioning

confidence: 99%

High-Fat Diet Causes Bone Loss in Young Mice by Promoting Osteoclastogenesis Through Alteration of the Bone Marrow Environment

et al. 2015

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Obesity is a severe health problem in children, afflicting several organ systems including bone. However, the role of obesity on bone homeostasis and bone cell function in children has not been studied in detail. Here we used young mice fed a high-fat diet (HFD) to model childhood obesity and investigate the effect of HFD on the phenotype of cells within the bone marrow environment. Five-week-old male mice were fed a HFD for 3, 6, and 12 weeks. Decreased bone volume was detected after 3 weeks of HFD treatment. After 6 and 12 weeks, HFD-exposed mice had less bone mass and increased osteoclast numbers. Bone marrow cells, but not spleen cells, from HFD-fed mice had increased osteoclast precursor frequency, elevated osteoclast formation and bone resorption activity, as well as increased expression of osteoclastogenic regulators including RANKL, TNF, and PPAR-gamma. Bone formation rate and osteoblast and adipocyte numbers were also increased in HFD-fed mice. Isolated bone marrow cells also had a corresponding elevation in the expression of positive regulators of osteoblast and adipocyte differentiation. Our findings indicate that in juvenile mice, HFD-induced bone loss is mainly due to increased osteoclast bone resorption by affecting the bone marrow microenvironment. Thus, targeting osteoclast formation may present a new therapeutic approach for bone complications in obese children. 5Co-corresponding author: Xing, Lianping,

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“…Increased marrow adiposity in obese mice is accompanied by decreases in trabecular bone volume and overall reduced BMD [61–63]. These structural changes are paralleled by increases in osteoclast activity, upregulation of bone-degrading proteases such as cathepsin K, and escalated levels of proinflammatory cytokines, such as interleukin 6 (IL-6) and tumor necrosis factor α, (TNF-α) [53, 61–65]. Unfortunately, due to lack of controlled studies on effects of obesity on bone health in humans, the relationship between adiposity and bone turnover remains complex and controversial.…”

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

confidence: 99%

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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Osteoclastogenesis by Bone Marrow-Derived Macrophages Is Enhanced in Obese Mice

Cited by 51 publications

References 36 publications

Advances in Osteoimmunology: Pathophysiologic Concepts and Treatment Opportunities

Advances in Osteoimmunology: Pathophysiologic Concepts and Treatment Opportunities

High-Fat Diet Causes Bone Loss in Young Mice by Promoting Osteoclastogenesis Through Alteration of the Bone Marrow Environment

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

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