Determinants of bone marrow adiposity: The modulation of peroxisome proliferator-activated receptor-γ2 activity as a central mechanism

Gijsen, Hanél Sadie-Van; Hough, F. S.; Ferris, William F.

doi:10.1016/j.bone.2013.06.016

Cited by 40 publications

(26 citation statements)

References 233 publications

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“…Bone marrow adiposity has been linked to changes in bone density, increased numbers of osteoclasts, fewer numbers of osteoblasts, and accelerated growth of prostate cancer in bone [33, 34]. We have shown previously that mice fed high fat diet (HFD) have more adipocytes in the bone marrow compared to low fat diet (LFD) control mice [20].…”

Section: Resultsmentioning

confidence: 99%

Marrow adipocyte-derived CXCL1 and CXCL2 contribute to osteolysis in metastatic prostate cancer

Hardaway

Herroon

Rajagurubandara

et al. 2015

Clin Exp Metastasis

124

112

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Increased bone marrow adiposity is a common feature of advanced age, obesity and associated metabolic pathologies. Augmented numbers of marrow adipocytes positively correlate with dysregulated bone remodeling, also a well-established complication of metastatic disease. We have shown previously that marrow adiposity accelerates prostate tumor progression in the skeleton and promotes extensive destruction of the bone; however, the factors behind adipocyte-driven osteolysis in the skeletal tumor microenvironment are not currently known. In this study, utilizing in vivo diet-induced models of bone marrow adiposity, we reveal evidence for positive correlation between increased marrow fat content, bone degradation by ARCaP(M) and PC3 prostate tumors, and augmented levels of host-derived CXCL1 and CXCL2, ligands of CXCR2 receptor. We show by in vitro osteoclastogenesis assays that media conditioned by bone marrow adipocytes is a significant source of CXCL1 and CXCL2 proteins. We also demonstrate that both the adipocyte-conditioned media and the recombinant CXCL1 and CXCL2 ligands efficiently accelerate osteoclast maturation, a process that can be blocked by neutralizing antibodies to each of the chemokines. We further confirm the contribution of CXCR2 signaling axis to adiposity-driven osteoclastogenesis by blocking fat cell-induced osteoclast differentiation with CXCR2 antagonist or neutralizing antibodies. Together, our results link CXCL1 and CXCL2 chemokines with bone marrow adiposity and implicate CXCR2 signaling in promoting effects of marrow fat on progression of skeletal tumors in bone.

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Section: Resultsmentioning

confidence: 99%

Marrow adipocyte-derived CXCL1 and CXCL2 contribute to osteolysis in metastatic prostate cancer

Hardaway

Herroon

Rajagurubandara

et al. 2015

Clin Exp Metastasis

124

112

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“…This mechanism for bone loss has been implicated in aging and thiazolidinedione use. Adipogenesis is regulated by several transcriptional factors, and peroxisome proliferator-activator receptor-γ (PPARγ) is thought to be of particular importance [25]. After differentiation, marrow adipocytes may directly influence bone metabolism.…”

Section: Marrow Fat Is Negatively Associated With Bonementioning

confidence: 99%

Diabetes and Bone Marrow Adiposity

Kim

Schafer

2016

Curr Osteoporos Rep

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Purpose of Review This study aims to describe bone marrow fat changes in diabetes and to discuss the potential role of marrow fat in skeletal fragility. Recent Findings Advances in non-invasive imaging have facilitated marrow fat research in humans. In contrast to animal studies which clearly demonstrate higher levels of marrow fat in diabetes, human studies have shown smaller and less certain differences. Marrow fat has been reported to correlate with A1c, and there may be a distinct marrow lipid saturation profile in diabetes. Summary Greater marrow fat is associated with impaired skeletal health. Marrow fat may be a mediator of skeletal fragility in diabetes. Circulating lipids, growth hormone alterations, visceral adiposity, and hypoleptinemia have been associated with greater marrow fat and may represent potential mechanisms for the putative effects of diabetes on marrow fat, although other factors likely contribute. Additional research is needed to further define the role of marrow fat in diabetic skeletal fragility and to determine whether marrow fat is a therapeutic target.

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“…This differentiation process is mainly regulated by the transcription factors PPAR␥ and runx2 (for adipogenesis and osteoblastogenesis respectively), with the cooperation of numerous other factors, in particular the Wnt pathway (14,15). In addition, fat and bone are increasingly recognized as being capable of mutual regulation (15,16). This process occurs in the bone marrow, and histomorphometric studies have shown a positive connection between bone marrow adiposity and osteoporosis (17,18).…”

mentioning

confidence: 97%

“…Aging and estrogen deficiency-two conditions pivotally involved in the pathophysiology of osteoporosis-are associated with lower osteogenic and greater adipogenic lineage commitment of MSC (12,13). This differentiation process is mainly regulated by the transcription factors PPAR␥ and runx2 (for adipogenesis and osteoblastogenesis respectively), with the cooperation of numerous other factors, in particular the Wnt pathway (14,15). In addition, fat and bone are increasingly recognized as being capable of mutual regulation (15,16).…”

mentioning

confidence: 98%

The Role of Bone Marrow Fat in Skeletal Health: Usefulness and Perspectives for Clinicians

Paccou

Hardouin

Cotten

et al. 2015

The Journal of Clinical Endocrinology &Amp; Metabolism

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We conclude that most human data demonstrate an inverse relationship between BMF and BMD, but data on the relationship with fractures are inconsistent and need further study. In daily practice, the usefulness for clinicians of assessing BMF using magnetic resonance imaging is still limited. However, the perspectives are exciting, particularly in terms of improving the diagnosis and management of osteoporosis.

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Determinants of bone marrow adiposity: The modulation of peroxisome proliferator-activated receptor-γ2 activity as a central mechanism

Cited by 40 publications

References 233 publications

Marrow adipocyte-derived CXCL1 and CXCL2 contribute to osteolysis in metastatic prostate cancer

Marrow adipocyte-derived CXCL1 and CXCL2 contribute to osteolysis in metastatic prostate cancer

Diabetes and Bone Marrow Adiposity

The Role of Bone Marrow Fat in Skeletal Health: Usefulness and Perspectives for Clinicians

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