Factors circulating in the blood of type 2 diabetes mellitus patients affect osteoblast maturation – Description of a novel in vitro model

Ehnert, Sabrina; Freude, Thomas; Ihle, Christoph; Mayer, L.; Braun, Bianca; Graeser, Jessica; Flesch, Ingo; Stöckle, Ulrich; Nüssler, Andreas K.; Pscherer, Stefan

doi:10.1016/j.yexcr.2014.12.011

Cited by 39 publications

(31 citation statements)

References 41 publications

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“…Our results showed that hOB from T2DM patients were negatively affected with respect to RUNX2 and OSX gene expression when subjected to high glucose alone or together with AGEs in the culture medium, which is consistent with the data reported by other authors [4–8]. Recently, a down-regulation in RUNX2 and OSX expression has been demonstrated in pre-osteoblastic SCP-1 cells treated with serum from T2DM patients [19]. However, an increase in the expression of these genes [9, 18] or no variation in the expression [20] have also been reported by other authors.…”

Section: Discussionsupporting

confidence: 92%

Influence of high glucose and advanced glycation end-products (ages) levels in human osteoblast-like cells gene expression

Miranda

Giner

Montoya

et al. 2016

BMC Musculoskelet Disord

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BackgroundType 2 diabetes mellitus (T2DM) is associated with an increased risk of osteoporotic fracture. Several factors have been identified as being potentially responsible for this risk, such as alterations in bone remodelling that may have been induced by changes in circulating glucose or/and by the presence of non-oxidative end products of glycosylation (AGEs). The aim of this study is to assess whether such variations generate a change in the gene expression related to the differentiation and osteoblast activity (OPG, RANKL, RUNX2, OSTERIX, and AGE receptor) in primary cultures of human osteoblast-like cells (hOB).MethodsWe recruited 32 patients; 10 patients had osteoporotic hip fractures (OP group), 12 patients had osteoporotic hip fractures with T2DM (T2DM group), and 10 patients had hip osteoarthritis (OA group) with no osteoporotic fractures and no T2DM. The gene expression was analyzed in hOB cultures treated with physiological glucose concentration (4.5 mM) as control, high glucose (25 mM), and high glucose plus AGEs (2 μg/ml) for 24 h.ResultsThe hOB cultures from patients with hip fractures presented slower proliferation. Additionally, the hOB cultures from the T2DM group were the most negatively affected with respect to RUNX2 and OSX gene expression when treated solely with high glucose or with high glucose plus AGEs. Moreover, high levels of glucose induced a major decrease in the RANKL/OPG ratio when comparing the OP and the T2DM groups to the OA group.ConclusionsOur data indicates an altered bone remodelling rate in the T2DM group, which may, at least partially, explain the reduced bone strength and increased incidence of non-traumatic fractures in diabetic patients.

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Section: Discussionsupporting

confidence: 92%

Influence of high glucose and advanced glycation end-products (ages) levels in human osteoblast-like cells gene expression

Miranda

Giner

Montoya

et al. 2016

BMC Musculoskelet Disord

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“…Animal models revealing both positive [3][4][5] and negative [6][7][8] effects of TGF-β 1 on bone strength have been reported. Likewise, poor bone quality and delayed fracture healing in patients is associated with both the lack of TGF-β 1 and chronically elevated TGF-β 1 levels [9][10][11][12][13][14][15]. We have recently shown that continuous exposure to human recombinant TGF-β 1 (rhTGF-β 1 ) inhibits bone morphogenetic protein (rhBMP2 and rhBMP7)-dependent maturation of primary human osteoblasts (hOBs) in a histone deacetylase (HDAC)-dependent manner [16].…”

Section: Introductionmentioning

confidence: 99%

TGF-β1-Dependent Downregulation of HDAC9 Inhibits Maturation of Human Osteoblasts

Ehnert¹,

Heuberger²,

Nüssler³

et al. 2017

JFMK

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Abstract:Transforming growth factor β (TGF-β) is a key regulator of bone density. Recently, we have shown that TGF-β 1 effectively blocks bone morphogenetic protein-induced maturation of human osteoblasts (hOBs) in a histone deacetylase (HDAC)-dependent manner. To better understand the underlying mechanisms and to identify possible therapeutic targets, the current study aimed at characterizing the expression changes of different HDACs in hOBs following recombinant human TGF-β 1 treatment and investigating the effect of the altered HDACs on both the proliferation and maturation of hOBs and osteogenic cell lines. As expected from our previous work, exposure to rhTGF-β 1 induced the expression of HDACs (HDAC1, -2, -3, -6). However, to our surprise, rhTGF-β 1 treatment strongly suppressed the expression of HDAC9 during osteogenic differentiation. HDAC9 is reported to suppress osteoclastogenesis; however, little is known about the role of HDAC9 in osteogenesis. Chemical inhibition of HDAC9 with TMP269 increased cell numbers of hOBs, but significantly decreased their osteogenic function (alkaline phosphatase activity and matrix mineralization). In osteogenic cell lines (MG-63, CAL-72 and SAOS-2), the expression of HDAC9 negatively correlates with their proliferation capacity and positively correlates with their osteogenic differentiation potential. Being able to boost osteoclasts while inhibiting osteoblasts makes HDAC9 an interesting therapeutic target to support fracture healing and bone metabolisms.Keywords: primary human osteoblasts (phOBs); transforming growth factor β 1 (TGF-β 1 ); histone deacetylase 9 (HDAC9)

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“…"c" indicates conflicting reports with respect to promotion or inhibition of metastasis. with no signs of malignant transformation and key features of SCP-1 are similar to primary MSC, including the capacity of multilineage differentiation [31,62] and establishment of cell-cell contact with hematopoietic cells [63]. Moreover, important signaling pathways that appeared in our network between MSC and HSPC, e.g.…”

Section: Potential Effects Of Bcc Signaling On the Hematopoietic Micrmentioning

confidence: 89%

Cell-Cell Communication Networks Propose a Modulation of the Hematopoietic Stem Cell Niche by Invading Breast Carcinoma Cells

Wobus¹,

W²

2015

J Bone Marrow Res

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Background: The human bone marrow can become a target of disseminated tumor cells in a relevant proportion of breast cancer patients. However, the underlying pathophysiology is incompletely understood. This study aims to identify and characterize potential mechanisms modulating the bone marrow hematopoietic microenvironment by invading breast cancer cells (BCC) as a basis for experimental evaluation.

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Factors circulating in the blood of type 2 diabetes mellitus patients affect osteoblast maturation – Description of a novel in vitro model

Cited by 39 publications

References 41 publications

Influence of high glucose and advanced glycation end-products (ages) levels in human osteoblast-like cells gene expression

Influence of high glucose and advanced glycation end-products (ages) levels in human osteoblast-like cells gene expression

TGF-β1-Dependent Downregulation of HDAC9 Inhibits Maturation of Human Osteoblasts

Cell-Cell Communication Networks Propose a Modulation of the Hematopoietic Stem Cell Niche by Invading Breast Carcinoma Cells

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