The dual role of BMP4 in adipogenesis and metabolism

Modica, Salvatore; Wolfrum, Christian

doi:10.1080/21623945.2017.1287637

Cited by 32 publications

(28 citation statements)

References 49 publications

(82 reference statements)

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“…BMP4 function in bone is complex. 36 Recently, it has been demonstrated that increased circulating levels of BMP4 in obese human subjects and diet-induced obesity (DIO) mice, 37,38 which is often accompanied with osteoporosis, suggesting a osteoporosis promotion role of BMP4. Furthermore, disruption of signalling through BMPR1A in adult osteoblasts or osteoclasts [39][40][41] increases bone mass provides evidence that alteration of the physiologic levels of BMPs and/or altering BMPR1A may have therapeutic effects on bone loss in vivo.…”

Section: Discussionmentioning

confidence: 99%

A Lox/CHOP‐10 crosstalk governs osteogenic and adipogenic cell fate by MSCs

Jiang

Xing

Wang

et al. 2018

J Cellular Molecular Medi

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Accelerated marrow adipogenesis has been associated with ageing and osteoporosis and is thought to be because of an imbalance between adipogenic and osteogenic differentiation of mesenchymal stem cell (MSCs). We have previously found that lysyl oxidase (Lox) inhibition disrupts BMP4‐induced adipocytic lineage commitment and differentiation of MSCs. In this study, we found that lox inhibition dramatically up‐regulates BMP4‐induced expression of CCAAT/enhancer binding protein (C/EBP) homologous protein 10 (CHOP‐10), which then promotes BMP4‐induced osteogenesis of MSCs both in vitro and in vivo. Specifically, Lox inhibition or CHOP‐10 up‐regulation activated Wnt/β‐catenin signalling to enhance BMP4‐induced osteogenesis, with pro‐adipogenic p38 MAPK and Smad signalling suppressed. Together, we demonstrate that Lox/CHOP‐10 crosstalk regulates BMP4‐induced osteogenic and adipogenic fate determination of MSCs, presenting a promising therapeutic target for osteoporosis and other bone diseases.

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Section: Discussionmentioning

confidence: 99%

A Lox/CHOP‐10 crosstalk governs osteogenic and adipogenic cell fate by MSCs

Jiang

Xing

Wang

et al. 2018

J Cellular Molecular Medi

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“…Transforming Growth Factor-β (TGF-β) family ligands, which include TGF-β, Activin, GDF, and BMP family growth factors, have known roles in both adipogenesis and adipocyte hypertrophy (Lee, 2018, Tang & Lane, 2012, Zamani & Brown, 2011. Thus, TGF-β1, GDF-8, and Activins A and B inhibit adipogenesis (Choy, Skillington et al, 2000, Hirai, Yamanaka et al, 2005, Hoggard, Cruickshank et al, 2009, Ignotz & Massague, 1985, Kim, Liang et al, 2001, Lee, Pickering et al, 2019, Luo, Guo et al, 2019, Sparks, Allen et al, 1992, whereas several BMPs have been shown to promote adipogenesis and/or adipocyte hypertrophy (Gustafson, Hammarstedt et al, 2015, Huang, Song et al, 2009, Modica & Wolfrum, 2017, Schreiber, Dorpholz et al, 2017, Tang, Otto et al, 2004, Tseng, Kokkotou et al, 2008. Yet in spite of a large body of work in this area, fundamental questions remain unresolved, including what steps of adipogenesis are regulated by specific TGF-β family pathways, how are intracellular signaling pathways activated to direct adipocyte development, and can extracellular TGF-β family inhibitors help control adipogenesis.…”

Section: Introductionmentioning

confidence: 99%

TGF-Β Family Inhibitors Blunt Adipogenesis Via Non-Canonical Regulation Of SMAD Pathways

Aykul

Maust

Floer

et al. 2020

Preprint

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Adipose tissues (AT) expand in response to energy surplus through adipocyte hypertrophy and hyperplasia (i.e., adipogenesis). The latter is a process by which multipotent precursors differentiate into mature adipocytes. This process is directed by growth factors and cytokines, including members of the TGF-β family, which regulate intracellular signaling pathways that control adipogenic transcriptional programs. As ectopic adipogenesis has been linked with metabolic syndrome and other pathological conditions, we undertook to establish how TGF-β family growth factors and their inhibitors regulate this process in a 3T3-L1 adipogenesis model. We found that intracellular SMAD1/5/8 signaling pathways are activated while SMAD2/3 pathways are suppressed in differentiating cells. Addition of SMAD1/5/8 pathway activating ligands promoted cell proliferation, while SMAD2/3 pathway activating ligands suppressed adipocyte formation. We identified several ligand traps that blunted 3T3-L1 adipogenesis. Strikingly, anti-adipogenic traps and ligands exploited the same mechanism of regulation involving a negative feedback loop that links SMAD2/3 activation with SMAD1/5/8 hyper-phosphorylation, cytoplasmic retention, and reduced signaling. The identified anti-adipogenic traps could be used to control hyperplastic AT expansion and its associated pathological conditions.

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“…Interestingly, BMP4 treatment suppressed UCP-1 expression while increasing lipid accumulation in brown preadipocytes [ 223 ]. However, the role of BMP4 on the differentiation of brown and beige adipocytes is controversial [ 252 ]…”

Section: Enzyme-linked Receptorsmentioning

confidence: 99%

Identification and characterization of adipose surface epitopes

Onogi

Khalil

Ussar

2020

Biochemical Journal

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Adipose tissue is a central regulator of metabolism and an important pharmacological target to treat the metabolic consequences of obesity, such as insulin resistance and dyslipidemia. Among the various cellular compartments, the adipocyte cell surface is especially appealing as a drug target as it contains various proteins that when activated or inhibited promote adipocyte health, change its endocrine function and eventually maintain or restore whole-body insulin sensitivity. In addition, cell surface proteins are readily accessible by various drug classes. However, targeting individual cell surface proteins in adipocytes has been difficult due to important functions of these proteins outside adipose tissue, raising various safety concerns. Thus, one of the biggest challenges is the lack of adipose selective surface proteins and/or targeting reagents. Here, we discuss several receptor families with an important function in adipogenesis and mature adipocytes to highlight the complexity at the cell surface and illustrate the problems with identifying adipose selective proteins. We then discuss that, while no unique adipocyte surface protein might exist, how splicing, posttranslational modifications as well as protein/protein interactions can create enormous diversity at the cell surface that vastly expands the space of potentially unique epitopes and how these selective epitopes can be identified and targeted.

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The dual role of BMP4 in adipogenesis and metabolism

Cited by 32 publications

References 49 publications

A Lox/CHOP‐10 crosstalk governs osteogenic and adipogenic cell fate by MSCs

A Lox/CHOP‐10 crosstalk governs osteogenic and adipogenic cell fate by MSCs

TGF-Β Family Inhibitors Blunt Adipogenesis Via Non-Canonical Regulation Of SMAD Pathways

Identification and characterization of adipose surface epitopes

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