scholarly journals Liraglutide Inhibits Osteoclastogenesis and Improves Bone Loss by Downregulating Trem2 in Female Type 1 Diabetic Mice: Findings From Transcriptomics

2021 ◽  
Vol 12 ◽  
Author(s):  
Jie Yu ◽  
Yan-Chuan Shi ◽  
Fan Ping ◽  
Wei Li ◽  
Hua-Bing Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Loss ◽  
Bone Quality ◽  
Normal Glucose Tolerance ◽  
Bone Fragility ◽  
Protective Effects ◽  
Mineral Density ◽  
Normal Glucose ◽  
Glucagon Like Peptide 1

BackgroundThe mechanisms of bone fragility in type 1 diabetes (T1D) are not fully understood. Whether glucagon-like peptide-1 receptor (GLP-1R) agonists could improve bone quality in T1D context also remains elusive.AimsWe aimed to explore the possible mechanisms of bone loss in T1D and clarify whether liraglutide has effects on bone quality of T1D mice using transcriptomics.MethodsFemale streptozotocin-induced diabetic C57BL/6J mice were randomly divided into four groups and received the following treatments daily for 8 weeks: saline as controls, insulin, liraglutide, and liraglutide combined with insulin. These groups were also compared with non-STZ-treated normal glucose tolerance (NGT) group. Trunk blood and bone tissues were collected for analysis. Three tibia from each of the NGT, saline-treated, and liraglutide-treated groups were randomly selected for transcriptomics.ResultsCompared with NGT mice, saline-treated T1D mice manifested markedly hyperglycemia and weight loss, and micro-CT revealed significantly lower bone mineral density (BMD) and deficient microarchitectures in tibias. Eight weeks of treatment with liraglutide alone or combined with insulin rescued the decreased BMD and partly corrected the compromised trabecular microarchitectures. Transcriptomics analysis showed there were 789 differentially expressed genes mainly mapped to osteoclastogenesis and inflammation pathways. The RT-qPCR verified that the gene expression of Trem2, Nfatc1, Trap, and Ctsk were significantly increased in the tibia of T1D compared with those in the NGT group. Liraglutide treatment alone or combined with insulin could effectively suppress osteoclastogenesis by downregulating the gene expression of Trem2, Nfatc1, Ctsk, and Trap.ConclusionsTaken together, increased osteoclastogenesis with upregulated expression of Trem2 played an important role in bone loss of T1D mice. Liraglutide provided protective effects on bone loss in T1D mice by suppressing osteoclastogenesis.

scholarly journals Serum Levels of miR-148a and miR-21-5p Are Increased in Type 1 Diabetic Patients and Correlated with Markers of Bone Strength and Metabolism

2018 ◽  
Vol 4 (4) ◽  
pp. 37 ◽  
Author(s):  
Giuseppina E. Grieco ◽  
Dorica Cataldo ◽  
Elena Ceccarelli ◽  
Laura Nigi ◽  
Giovanna Catalano ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Type 1 Diabetes ◽  
Bone Loss ◽  
Bone Metabolism ◽  
Bone Remodeling ◽  
Bone Mineral ◽  
Bone Fragility ◽  
Bone Homeostasis ◽  
Mineral Density

Type 1 diabetes (T1D) is characterized by bone loss and altered bone remodeling, resulting into reduction of bone mineral density (BMD) and increased risk of fractures. Identification of specific biomarkers and/or causative factors of diabetic bone fragility is of fundamental importance for an early detection of such alterations and to envisage appropriate therapeutic interventions. MicroRNAs (miRNAs) are small non-coding RNAs which negatively regulate genes expression. Of note, miRNAs can be secreted in biological fluids through their association with different cellular components and, in such context, they may represent both candidate biomarkers and/or mediators of bone metabolism alterations. Here, we aimed at identifying miRNAs differentially expressed in serum of T1D patients and potentially involved in bone loss in type 1 diabetes. We selected six miRNAs previously associated with T1D and bone metabolism: miR-21; miR-24; miR-27a; miR-148a; miR-214; and miR-375. Selected miRNAs were analyzed in sera of 15 T1D patients (age: 33.57 ± 8.17; BMI: 21.4 ± 1.65) and 14 non-diabetic subjects (age: 31.7 ± 8.2; BMI: 24.6 ± 4.34). Calcium, osteocalcin, parathormone (PTH), bone ALkaline Phoshatase (bALP), and Vitamin D (VitD) as well as main parameters of bone health were measured in each patient. We observed an increased expression of miR-148a (p = 0.012) and miR-21-5p (p = 0.034) in sera of T1D patients vs non-diabetic subjects. The correlation analysis between miRNAs expression and the main parameters of bone metabolism, showed a correlation between miR-148a and Bone Mineral Density (BMD) total body (TB) values (p = 0.042) and PTH circulating levels (p = 0.033) and the association of miR-21-5p to Bone Mineral Content-Femur (BMC-FEM). Finally, miR-148a and miR-21-5p target genes prediction analysis revealed several factors involved in bone development and remodeling, such as MAFB, WNT1, TGFB2, STAT3, or PDCD4, and the co-modulation of common pathways involved in bone homeostasis thus potentially assigning a role to both miR-148a and miR-21-5p in bone metabolism alterations. In conclusion, these results lead us to hypothesize a potential role for miR-148a and miR-21-5p in bone remodeling, thus representing potential biomarkers of bone fragility in T1D.

scholarly journals MECHANISMS IN ENDOCRINOLOGY: Mechanisms and evaluation of bone fragility in type 1 diabetes mellitus

2016 ◽  
Vol 174 (4) ◽  
pp. R127-R138 ◽  
Author(s):  
F S Hough ◽  
D D Pierroz ◽  
C Cooper ◽  
S L Ferrari ◽  
_ _
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Bone Fragility ◽  
Mineral Density ◽  
Good Glycaemic Control ◽  
Marrow Adiposity ◽  
Igf1 Deficiency

Subjects with type 1 diabetes mellitus (T1DM) have decreased bone mineral density and an up to sixfold increase in fracture risk. Yet bone fragility is not commonly regarded as another unique complication of diabetes. Both animals with experimentally induced insulin deficiency syndromes and patients with T1DM have impaired osteoblastic bone formation, with or without increased bone resorption. Insulin/IGF1 deficiency appears to be a major pathogenetic mechanism involved, along with glucose toxicity, marrow adiposity, inflammation, adipokine and other metabolic alterations that may all play a role on altering bone turnover. In turn, increasing physical activity in children with diabetes as well as good glycaemic control appears to provide some improvement of bone parameters, although robust clinical studies are still lacking. In this context, the role of osteoporosis drugs remains unknown.

scholarly journals Insight into Bone Protective Mechanisms of Dried Plum Using an Ovariectomized Rat Model (OR18-06-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Bahram Arjmandi ◽  
Neda Akhavan ◽  
Joseph Munoz ◽  
Kelli George ◽  
Elizabeth Foley ◽  
...  
Keyword(s):  
Bone Loss ◽  
Postmenopausal Women ◽  
Bone Mineral ◽  
Rat Model ◽  
Bone Histomorphometry ◽  
Hormone Deficiency ◽  
Ovarian Hormone ◽  
Protective Effects ◽  
Mineral Density ◽  
Funding Sources

Abstract Objectives Osteoporosis may result in fracture with dire consequences. For instance, 40% of people with their second hip fracture die within two years. Aside from pharmaceutical interventions, that are not free of side effects, identifying edible and safe foods to prevent bone loss is of importance. We and others have shown that dried plum (DP) prevents loss of bone both in ovariectomized (Ovx) rat models as well as postmenopausal women. Hence, the purpose of this study was to examine the bone protective mechanism of action of DP, a rich source of phenolic and flavonoid compounds, in preventing bone loss using a rat model of ovarian hormone deficiency. Methods Forty-eight 90-day old female Sprague-Dawley rats were divided into four groups: sham-operated (Sham), Ovx, Ovx + 5% DP (low-dose, LD), and Ovx + 25% DP (high-dose, HD). Treatments started immediately after surgery and continued for 45 days. Animals were either fed a semi-purified diet, or a similar diet in which 5% or 25% of the diet (w/w) consisted of DP. All diets were made isocaloric and isonitrogenous containing 0.4% calcium and 0.3% phosphorus. Food intake, bone mineral density, bone mineral content, body/organ weight, blood biomarkers of bone metabolism, and static bone histomorphometry were assessed. Results The right femoral and the 4th lumbar vertebrae density were significantly (P < 0.05) lower in the Ovx control rats compared to Sham. The loss of density in both bones were completely prevented by HD-DP (P < 0.05). The HD-DP increased insulin-like growth factor-1 (IGF-1) significantly (P < 0.05) from 110 ± 4 ηmol/L to 135 ± 4 ηmol/L. In terms of bone histomorphometry, % bone area was significantly (P < 0.05) decreased as a result of Ovx and HD-DP nearly prevented this decrease (P > 0.05). Although the endosteal perimeter (mm2) was not statistically different from other groups, the endosteal perimeter of the HD-DP group was 13.6% lower than that of the Ovx group. Conclusions The bone protective effects of DP may, in part, be explained by an increase in IGF-1, which is strongly correlated with bone formation, and a decrease in the endosteal perimeter, which is increased in ovarian hormone deficiency and postmenopausal women. Future studies should examine radiolabeling compounds in DP to see how they contribute to its bone protective effects. Funding Sources There have been no funding sources.

Protective effects of the angiotensin type 1 receptor antagonist losartan in infection-induced and arthritis-associated alveolar bone loss

2015 ◽  
Vol 50 (6) ◽  
pp. 814-823 ◽  
Author(s):  
C. M. Queiroz-Junior ◽  
K. D. Silveira ◽  
C. R. de Oliveira ◽  
A. P. Moura ◽  
M. F. M. Madeira ◽  
...  
Keyword(s):  
Bone Loss ◽  
Receptor Antagonist ◽  
Alveolar Bone ◽  
Alveolar Bone Loss ◽  
Protective Effects ◽  
Angiotensin Type

scholarly journals Diabetes mellitus and osteoporosis: pathogenetic relationship and current principles of treatment

2021 ◽  
pp. 96-107
Author(s):  
T. Y. Demidova ◽  
V. M. Plakhotnyaya
Keyword(s):  
Diabetes Mellitus ◽  
Bone Matrix ◽  
Wnt Signaling Pathway ◽  
Bone Fragility ◽  
Current Data ◽  
Mineral Density ◽  
Increased Risk ◽  
Dm Type 2

Diabetes mellitus (DM) is a well known risk factor for osteoporosis and an increased risk of fractures. A lot of data has been published about the relationship between diabetes and bone health. DM type 1 and DM type 2 have different effects on bone mineral density (BMD). The central link in pathogenesis of bone fragility in patients with DM type 1 is a violation of the activity and gifferentiation of osteoblasts. On the contrary, hyperinsulinemia in DM type 2 activates the division and gifferentiation of osteoblasts and contributes to an increase in BMD. However, Higher BMD values in patients with DM type 2 are combined with slowdown in bone metabolism. As the result, high-quality bone remodeling does not occur. And bone strength decreases despite the high BMD. Despite the differences, DM type 1 and DM type 2 have common pathogenic pathways, that lead to increased bone fragility. For example, non-enzymatic glycation of bone matrix collagen and increase in concentration of sclerostin, which blocks the Wnt signaling pathway. In this review, we will analyze current data about epidemiology and pathogenesis of osteoporosis in DM and discuss the practical issues of the clinic, diagnosis, stratification of fracture risk and treatment. Special attention will be paid to the effects of glucose-lowering and anti-osteoporotic drugs on bone tissue.

scholarly journals DIAGNOSIS OF ENDOCRINE DISEASE: Evaluation of bone fragility in endocrine disorders

2019 ◽  
Vol 180 (6) ◽  
pp. R213-R232 ◽  
Author(s):  
Cristina Eller-Vainicher ◽  
Alberto Falchetti ◽  
Luigi Gennari ◽  
Elisa Cairoli ◽  
Francesco Bertoldo ◽  
...  
Keyword(s):  
Bone Density ◽  
Fracture Risk ◽  
Bone Quality ◽  
Risk Estimation ◽  
Underlying Disease ◽  
Bone Fragility ◽  
Endocrine Disorders ◽  
Mineral Density ◽  
Endocrine Diseases ◽  
Density Evaluation

An underlying disease affecting bone health is present in up to 40 and 60% of osteoporotic postmenopausal women and men respectively. Among the disorders leading to a secondary form of osteoporosis, the endocrine diseases are highly represented. A frequent finding in patients affected with an endocrine-related forms of bone disease is that the skeletal fragility is partially independent of the bone density, since the fracture risk in these patients is related more to a reduction of bone quality than to a decrease of bone mass. As a consequence, bone mineral density evaluation by dual-X-ray absorptiometry may be inadequate for establishing the risk of fracture in the setting of the endocrine-related forms of osteoporosis. In the recent years, several attempts to non-invasively estimating bone quality have been done. Nowadays, some new tools are available in the clinical practice for optimising the fracture risk estimation in patients with endocrine disorders. The aim of this review is to summarise the evidence regarding the role of the different imaging tools for evaluating bone density and bone quality in the most frequent forms of endocrine-related osteoporosis, such as obesity, diabetes, acromegaly, thyrotoxicosis, primary hyperparathyroidism, hypercortisolism and hypogonadism. For each of these disorders, data regarding both the current available tools and the future possible new techniques for assessing bone fragility in patients with endocrine diseases are reported.

scholarly journals The combined effects of soya isoflavones and resistant starch on equol production and trabecular bone loss in ovariectomised mice

2016 ◽  
Vol 116 (2) ◽  
pp. 247-257 ◽  
Author(s):  
Yuko Tousen ◽  
Yu Matsumoto ◽  
Chiho Matsumoto ◽  
Yoriko Nishide ◽  
Yuya Nagahata ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Bone Loss ◽  
Intestinal Microbiota ◽  
Resistant Starch ◽  
Combined Effects ◽  
Mineral Density ◽  
Inflammatory Gene Expression ◽  
Cytokine Levels ◽  
Trabecular Bone Loss

AbstractEquol is a metabolite of the soya isoflavone (ISO) daidzein that is produced by intestinal microbiota. Equol has greater oestrogenic activity compared with other ISO, and it prevents bone loss in postmenopausal women. Resistant starch (RS), which has a prebiotic activity and is a dietary fibre, was reported to promote equol production. Conversely, the intestinal microbiota is reported to directly regulate bone health by reducing inflammatory cytokine levels and T-lymphocytes in bone. The present study evaluated the combined effects of diet supplemented with ISO and RS on intestinal microbiota, equol production, bone mineral density (BMD) and inflammatory gene expression in the bone marrow of ovariectomised (OVX) mice. Female ddY strain mice, aged 8 weeks, were either sham-operated (Sham, n 7) or OVX. OVX mice were randomly divided into the following four groups (seven per group): OVX control (OVX); OVX fed 0·05 % ISO diet (OVX+ISO); OVX fed 9 % RS diet (OVX+RS); and OVX fed 0·05 % ISO- and 9 % RS diet (OVX+ISO+RS). After 6 weeks, treatment with the combination of ISO and RS increased equol production, prevented the OVX-induced decline in trabecular BMD in the distal femur by modulating the enteric environment and altered OVX-induced inflammation-related gene expression in the bone marrow. However, there were no significant differences in bone parameters between the ISO+RS and ISO-alone groups in OVX mice. Our findings suggest that the combination of ISO and RS might alter intestinal microbiota and immune status in the bone marrow, resulting in attenuated bone resorption in OVX mice.

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