The Janus face of OSM-mediated cardiomyocyte dedifferentiation during cardiac repair and disease

Pöling, Jochen; Gajawada, Praveen; Lörchner, Holger; Polyakova,; Szibor, Marten; Böttger, T; Warnecke, H.; Kubin, Thomas; Braun, Thomas

doi:10.4161/cc.11.3.19024

Cited by 35 publications

(44 citation statements)

References 23 publications

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“…Similarly, significant accumulation of FGF23 was observed in cardiomyocytes of patients with myocarditis, ischemic and dilative cardiomyopathy. We therefore suggest the following mechanism of FGF23 expression and secretion: Monocytes/macrophages invade the myocardium after an initial injury and release oncostatin M which induces a "cell survival program" via the oncostatin M receptor-β [6,9]. Under chronic extension of low level inflammation cardiomyocytes are constantly stimulated and produce FGF23 even if the myocardial performance deteriorates.…”

Section: Discussionmentioning

confidence: 99%

“…They convincingly demonstrate that the over expression or mutation of a single cytokine/ chemokine/growth factor, a corresponding receptor or intracellular signalling molecule is sufficient to evoke HF [5][6][7]. However, these signalling cascades are not detrimental per se but constitute an evolutionary conserved defence mechanism [6,8,9]. Since the initiated "cell survival program" might turn into a "cell death program" by chronic activation, the blockade of cytokine/growth factor controlling signalling cascades becomes a promising therapeutic strategy.…”

Section: Introductionmentioning

confidence: 99%

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Oncostatin M Induces FGF23 Expression in Cardiomyocytes

Richter¹,

Polyakova²,

Gajawada³

2012

J Clin Exp Cardiolog

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Background: It is well-known that elevated levels of Fibroblast Growth Factor-23 (FGF23), a bone derived hormone, in circulation are associated with renal failure. Recent studies emphasize the correlation between Heart Failure (HF) and FGF23, but the ability of cardiomyocytes themselves to express and secrete this phosphatonin is yet unknown. A further factor involved in HF is the cytokine oncostatin M (OSM). The aims of our study were: 1) to analyze the myocardium of HF patients in terms of FGF23 expression in cardiomyocytes and 2) to assess whether OSM is able to induce FGF23 production in cardiomyocytes. Methods:Cultures of adult cardiomyocytes were treated with OSM and screened for the expression of FGF23 transcripts. FGF23 secretion was determined by Western blot and ELISA of cell culture supernatants. Heart explants of HF patients with Dilated Cardiomyopathy (DCM), Ischemic Cardiomyopathy (ICM) and myocarditis (Myo) were analyzed by immunofluorescence using FGF23 antibodies and compared with healthy controls. FGF23 levels were also determined in mice with a cardiac restricted overexpression of Monocyte Chemotactic Protein-1 (MCP1), which developed an "inflammatory" Heart Failure (iHF) due to macrophage infiltration.Results: OSM massively induced the expression and secretion of FGF23 in cultured adult cardiomyocytes. Confocal microscopy revealed high amounts of FGF23 positive cardiomyocytes in the myocardium of patients with ischemic heart disease (IHD), myocarditis, dilated cardiomyopathy (DCM) and in mice with iHF. Conclusions:The presence of FGF23 in the myocardium of patients with different types of HF and in mice with "inflammatory" HF suggests that macrophages are responsible for the FGF23 expression in cardiomyocytes via OSM. Whether FGF23 acts as a regeneration promoting factor and/or potentially serves as a HF/transplantation marker has to be clarified.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Oncostatin M Induces FGF23 Expression in Cardiomyocytes

Richter¹,

Polyakova²,

Gajawada³

2012

J Clin Exp Cardiolog

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“…It was first identified as a secreted product of macrophage-like cells that inhibited proliferation of melanoma-, neuroblastoma-, and lung cancer-derived cell lines (2), and although it suppresses breast cancer cell proliferation (3), it has been suggested to support metastasis of breast cancer in the skeleton due to proosteoclastic activities (4) and to stimulate Kaposi's sarcoma (5). Studies in knock-out mice have shown that OSM supports hematopoiesis (6) and bone formation at the expense of adipogenesis (7), but it has also been implicated in pulmonary tissue fibrosis (8), cardiac disease and repair (9), prostate cancer (10), asthma (11), periodontal disease (12), and both rheumatoid and osteoarthritis (13).…”

Section: Oncostatin M (Osm)mentioning

confidence: 99%

Murine Oncostatin M Acts via Leukemia Inhibitory Factor Receptor to Phosphorylate Signal Transducer and Activator of Transcription 3 (STAT3) but Not STAT1, an Effect That Protects Bone Mass

Walker

Johnson

et al. 2016

Journal of Biological Chemistry

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“…In contrast to these early roles, OSM also has stimulatory roles in a number of human cancers including Kaposi's sarcoma 2 and breast cancer. 3 Frequently acting in conjunction with inflammatory factors or other gp130-dependent cytokines, OSM has been implicated in diverse disorders including pulmonary tissue fibrosis, 4 cardiac disease and repair, 5 prostate cancer, 6 asthma, 7 periodontal disease 8 and both rheumatoid arthritis and osteoarthritis. 9 In the context of skeletal biology, OSM is of particular interest as it displays anabolic effects on both cortical and trabecular bone (which would be clinically desirable to emulate) while at the same time driving osteoclast formation; notably, both influences are at least in part mediated by OSM action on the osteoblast lineage.…”

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Osteoimmunology: oncostatin M as a pleiotropic regulator of bone formation and resorption in health and disease

Sims

Quinn

2014

BoneKEy Reports

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Bone remodeling in health and disease is carried out by osteoblasts and osteoclasts, which respectively produce bone matrix and resorb it. Endocrine and paracrine control of these cells can be direct, but they are also exerted indirectly, either by influencing progenitor cell differentiation or by stimulating paracrine signals from local accessory cells including osteocytes (which form a critical communication and regulation network within the bone matrix), macrophages and T lymphocytes. Here we review the osteotropic actions of the interleukin-6 family member cytokine oncostatin M (OSM), which is of particular interest because of its ability to stimulate bone accrual. OSM is produced within the bone microenvironment by cells of both mesenchymal and hematopoietic origin, including osteocytes, osteoblasts, macrophages and T lymphocytes, and can act via two receptor complexes: OSM receptor:gp130 and leukemia inhibitory factor receptor (LIFR):gp130. Although OSM can directly stimulate osteoblast mineralization activity and differentiation, it can also stimulate mesenchymal stem cell osteoblastic commitment at the expense of adipogenesis. In osteocytes, OSM can suppress the production of the bone formation inhibitor sclerostin, an action that is mediated by LIFR:gp130. OSM also stimulates the production of receptor activator of nuclear factor kB ligand by osteoblasts and thereby drives the formation of osteoclasts particularly in pathological conditions. Thus, cellular effects of OSM on bone metabolism include direct and indirect actions mediated by two related receptor/ligand complexes. OSM therefore provides an example of paracrine and endocrine control mechanisms that regulate bone mass by controlling both bone formation and resorption.

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The Janus face of OSM-mediated cardiomyocyte dedifferentiation during cardiac repair and disease

Abstract: (2012) The Janus face of OSM-mediated cardiomyocyte dedifferentiation during cardiac repair and disease, Cell Cycle, 11:3,[439][440][441][442][443][444][445]

Cited by 35 publications

References 23 publications

Oncostatin M Induces FGF23 Expression in Cardiomyocytes

Oncostatin M Induces FGF23 Expression in Cardiomyocytes

Murine Oncostatin M Acts via Leukemia Inhibitory Factor Receptor to Phosphorylate Signal Transducer and Activator of Transcription 3 (STAT3) but Not STAT1, an Effect That Protects Bone Mass

Osteoimmunology: oncostatin M as a pleiotropic regulator of bone formation and resorption in health and disease

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