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Total versus uc-dpMGP: Associations with cardiovascular parameters

Authors:
Taken together, the results provide evidence for the protective effect
of nacre on post-menopausal-induced bone loss.
doi:10.1016/j.bonr.2020.100479
P153
Body composition and anthropometric data - inuence of total
and uc-dpMGP
Natascha Schweighofer
a,b
, Moritz Strasser
c
, Christoph W. Haudum
a,b
,
Albrecht Schmidt
d
, Ines Mursic
d
, Burkert Pieske
d
, Thomas R. Pieber
a,b
,
Barbara Obermayer-Pietsch
a
a
Dept. of Internal Medicine, Division of Endocrinology and Diabetology,
Medical University of Graz, Graz, Austria
b
CBmed, Center for Biomarker Research in Medicine, Graz, Austria
c
Department of Health Studies, Institute of Biomedical Science,
FH JOANNEUM, University of Applied Sciences, Graz, Austria
d
Dept. of Internal Medicine, Division of Cardiology, Medical University of
Graz, Graz, Austria
Body composition inuences the development of type 2 diabetes
mellitus (T2DM) and cardiovascular risk. According to literature,
matrix-GLA-protein (MGP) is associated with bone parameters and
cardiovascular risk in persons with and without T2DM. We investigated
whether uncarboxylated, dephosphorylated MGP (uc-dpMGP),
totalMGP or both are associated with body composition and
anthropometric parameters in patients with and without T2DM.
We analysed data from the BioPersMed cohort (n=966, 531 females,
435 males, mean age 58 ± 9 years, 255 without and 71 with T2DM), a
prospective cohort of asymptomatic subjects at cardiovascular risk.
T2DM was dened according to ADA criteria. Uc-dpMGP was measured
with IDS-iSYS InaKtif MGP Kit, totalMGP using the Human MGP(Matrix
Gla protein) ELISA Kit (Wuhan Fine Biotech Co., Ltd. China). Body
composition was determined by Lunar iDXA (GE Healthcare GmbH,
Austria).
Totalanduc-dpMGPdidnotcorrelatewitheachotherinbothsubject
groups.
Uc-dpMGP correlated positively with BMI (pb0.001), weight
(p=0.003), systolic/diastolic blood pressure (p=0.021 and 0.004,
respectively), heart frequency (p=0.011) and waist and hip
circumferences (both pb0.001) in subjects without T2DM and with
BMI (p=0.016), weight (p=0.021) and waist and hip circumferences
(p=0.025 and 0.046) in T2DM. TotalMGP showed no correlations with
these parameters in both subject groups.
Only in subjects without T2DM uc-dpMGP correlated positively with
total fat mass (pb0.001), total tissue mass (p=0.001), total overall mass
(p=0.002) and total tissue fat (pb0.001). No correlations were seen
with lean, fat free or bone mass. TotalMGP showed no associations with
body composition parameters in both subject groups.
Only uc-dpMGP correlated with anthropometric parameters in
diabetic and non-diabetic subjects, and with body composition in
subjects without diabetes.
Since MGP is expressed in fat tissue, uc-dpMGP might be a modulator
of body composition and fat distribution, and thus inuence T2DM and
cardiovascular risk development.
doi:10.1016/j.bonr.2020.100480
P154
Total versus uc-dpMGP: Associations with cardiovascular parameters
Natascha Schweighofer
a,b
, Moritz Strasser
c
, Christoph W. Haudum
a,b
,
Albrecht Schmidt
d
, Ewald Kolesnik
d
, Burkert Pieske
d
,
Thomas R. Pieber
a,b
, Barbara Obermayer-Pietsch
b
a
CBmed, Center for Biomarker Research in Medicine, Graz, Austria
b
Department of Internal Medicine, Division of Endocrinology and
Diabetology, Medical University of Graz, Graz, Austria
c
Department of Health Studies, Institute of Biomedical Science, FH
JOANNEUM, University of Applied Sciences, Graz, Austria
d
Department of Internal Medicine, Division of Cardiology, Medical
University of Graz, Graz, Austria
Vascular calcication, modulated i. a. by Matrix-GLA-protein
(MGP), is a risk factor for cardiovascular disease. We investigated
whether uncarboxylated, dephosphorylated MGP (uc-dpMGP),
totalMGP or both are associated with pulse wave velocity (PWV),
intima-media thickness (IMT) and relative wall thickness (RWT) in
patients with and without type 2 diabetes (T2DM).
We analysed data from the BioPersMed cohort (255 participants
without and 71 with T2DM, age 58 ± 9 years,), a prospective cohort
of asymptomatic participants at cardiovascular risk. T2DM was
dened according to ADA criteria. Uc-dpMGP was measured by
IDS-iSYS InaKtif MGP Kit, totalMGP by Human MGP(Matrix Gla
protein) ELISA Kit (Wuhan Fine Biotech Co., Ltd., China). Pulse wave
analysis was done with a SphygmoCor device (Atcor Medical,
Australia), IMT and echocardiograpy with the Vivid 9 device (GE
Healthcare Austria GmbH & Co OG, Austria).
Total and uc-dpMGP did not correlate with each other in both
participant groups. Uc-dpMGP was associated with BMI (pb0.001),
weight (p=0.003), systolic/diastolic blood pressure (p=0.021 and
0.004, respectively), heart frequency (p=0.011) and waist and hip
circumferences (both pb0.001) in participants without T2DM and
with BMI (p=0.016), weight (p=0.021) and waist and hip
circumferences (p=0.025 and 0.046) in participants with T2DM.
TotalMGP showed no correlations with these parameters in both
participant groups.
In participants without T2DM only uc-dpMGP correlated with
PWV and IMT (p=0.004 and p=0.001, respectively). Elevated uc-
dpMGP levels were seen in participants with end organ damage
compared to participants without (p=0.021). Only uc-dpMGP
associated with RWT groups (p=0.039) in non-diabetics. Higher
uc-dpMGP levels were found in participants with eccentric
compared to concentric cardiac hypertrophy.
Uc-dpMGP but not totalMGP was associated with cardiovascular
parameters only in participants without T2DM.
BV/TV of the trabecular bone at the femoral head after 4 weeks of nutritional
supplementation.
Abstracts 47
Our data implicate that uc-dpMGP is also an active MGP form and
might be a cardiovascular risk modulator, which needs further
investigation.
doi:10.1016/j.bonr.2020.100481
P155
High fat diet (HFD)-induced obesity augments the deleterious effects
of estrogen deciency in bone. Evidence from post-menopausal mice
Dalia Ali
a
, Florence Figeac
a
, Michaela Tencerova
b
, Nicholas Ditzel
a
,
Alexander Raunch
a
, Clarissa Schmal
a
, Moustapha Kassem
a,c
a
Department of Endocrinology and Metabolism, Molecular Endocrinology
& Stem Cell Research Unit (KMEB), University of Southern Denmark and
Odense University Hospital, Odense, Denmark
b
Molecular Physiology of Bone, Czech Academy of Sciences/Institute of
Physiology, Prague, Czech Republic
c
Department of Cellular and Molecular Medicine, University of Copenhagen/
Danish Stem Cell Centre, Copenhagen, Denmark
Male mice and human studies revealed that high fat diet (HFD)-
induced obesity exerted deleterious impact on skeletal stem cells
function yet limited studies have paid attention to sexual dysmorphism
and its impact on the cellular mechanisms linking obesity, menopause,
bone marrow adiposity and bone fragility. Female mice (C57BL/6J)
were ovariectomized (OVX) or Sham operated and were fed either HFD
or normal diet (ND) for 12 weeks. Mice fed with HFD showed a
signicant increase in body weight (~86% in HFD and ~122% in HFD-
OVX, pb0.0005) and impaired glucose tolerance. MicroCT-scanning
revealed negative impact of HFD-induced obesity on Tb.BV/TV (-15±
0.004% in HFD, pb0.05 and -37.5±0.005% in HFD-OVX, pb0.005) and
Tb-N (-13.8±0.063% in HFD, pb0.005, -23±0.056% in HFD-OVX, pb
0.0005) while Tb-Sep increased (+16.2±0.007% in HFD, pb0.005, +
31.8±0.008% in HFD-OVX, pb0.0005). In cortical bone, HFD-OVX
decreased cortical thickness (-13±0.003%, pb0.005) and increased
cortical porosity (+60.7±0.47%, pb0.005). HFD-induced expansion of
marrow adipose tissue (MAT) (+60.7±9.9%, pb0.05) was more
pronounced in HFD-OVX (+79.5±4.8%, pb0.005). Gene expression
analysis of whole bone, revealed that HFD and HFD-OVX exhibited up
regulation in adipogenesis (~2-8 fold), inammation (~2-13 fold) and
senescence gene expression markers (~2 fold). HFD-induced obesity
lead to bone loss, bone marrow adiposity expansion and up-regulation
of inammatory and senescence associated phenotype marker genes in
bone micro-environment. These effects are more pronounced by
estrogen deciency. Thus, obesity is not protective but augments the
negative effects of estrogen deciency on the skeleton.
doi:10.1016/j.bonr.2020.100482
P160
Contribution of PD-L1 expression to the energy metabolism of
mesenchymal stromal cells
Antoine Boutin
a
, ElHadji Djite
a
, Abigaïl Mazzu
a
, Didier Pisani
a
,
Abdel Wakkach
a
, Nathalie Mazure
b
, Claudine Blin-Wakkach
a
,
Matthieu Rouleau
a
a
Université Côte d'Azur, CNRS UMR 7370, Laboratoire de PhysioMédecine
Moléculaire, Nice, France
b
Université Côte d'Azur, INSERM U1065, C3M, Nice, France
Bone marrow mesenchymal stromal cells (MSCs) present strong
immunosuppressive properties, driving immune responses toward
regulation/tolerance. Despite these functions, clinical trials have shown
inconsistent efcacy of MSCs due in part to the lack of uniform cell
populations. Homogeneous well-characterized cells can be derived in
vitro from human induced pluripotent stem cells. We recently
characterized huiPS-MSCs immunosuppressive properties showing
their capacity to induce CD4+ T regulatory cells (Treg).
Immuno-metabolism studies have shown that depriving the
microenvironment from glucose (such as an exacerbated glycolytic
metabolism in tumor cells) participate to the differentiation of Treg
cells. PD-L1 has been involved in controlling such a glycolytic pathway
in tumor cells. Because MSCs use PD-L1 to inhibit PD1-expressing T
cells, we wondered whether such PD-L1/PD1 interaction could control
the energy metabolism of MSCs.
We analyzed the metabolism of MSCs licensedby TNF-a required
to induce PD-L1 expression. Our results presented in the gure indicate
that licensed MSCs might rely less on glycolysis and OxPhos for their
energetic metabolism. But, if PD-L1 is stimulated on such licensed MSCs
(use of an Fc-PD1 fusion protein), both the glycolysis and respiration of
MSCs are largely increased. This indicating that the interaction of PD-L1
with its ligand (PD1) results in a strong metabolic activation of MSCs
which could lead to an nutriment-deprived local micro-environment.
The molecular pathways involved are under investigation.
Our results bring new insights into the understanding of the metabolic
pathways controlled by the PD-L1 receptor on MSCs, contributing to their
better characterization for optimal clinical applications.
doi:10.1016/j.bonr.2020.100483
P161
Characterization and impact on osteogenesis of the extracellular
matrix of Bone Marrow Adipocytes in hyperglycemic condition
in vitro
Laura Entz
a
, Guillaume Falgayrac
b
, Christophe Chauveau
a
,
Gilles Pasquier
b,c
, Stéphanie Lucas
a
a
MABLab, ULCO University, Boulogne-sur-Mer Cedex, France
b
MABLab, Lille University, Lille, France
c
Orthopaedic surgery, Lille University Hospital, Lille, France
Withinthebonemarrow,theExtraCellular Matrix (ECM) produced by
surrounding cells such as Bone Mesenchymal Stromal Cells (BMSCs)
alters osteoblastogenesis. Since Bone Marrow Adipocyte (BMAd) quantity
and activity are modied with chronic hyperglycemia, we hypothesize
that BMAds produce a specic ECM which, upon exposure to a high
concentration of glucose, could be deleterious for bone quality in type 2
diabetes. The aims of this study are to characterize the BMAd ECM and to
evaluate its effect on osteogenic differentiation using in vitro approaches.
Human primary BMSCs (RoosterBio) were either cultured or
differentiated into BMAds or osteoblasts (OB) for 21 days in 5mM (LG)
Abstracts48
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