Novel insights into the complex architecture of osteoporosis molecular genetics

Saad, Fawzy A.

doi:10.1111/nyas.14231

Cited by 43 publications

(33 citation statements)

References 186 publications

(201 reference statements)

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“…Myostatin can inhibit osteogenic differentiation of BMSCs, as well as osteoblast differentiation and mineralization (Hamrick et al, 2007;Chen et al, 2017). Likewise, myostatin may inhibit osteogenesis by activating the RANKL signaling pathway, thus showing an adverse impact on bone mass (Saad, 2020). In addition, myostatin itself is an important autocrine/paracrine factor that inhibits skeletal muscle growth (Rodriguez et al, 2014;Cui et al, 2020).…”

Section: Elderly Patients With Obesitymentioning

confidence: 99%

Obesity and Bone Health: A Complex Link

Hou

et al. 2020

Front. Cell Dev. Biol.

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So far, the connections between obesity and skeleton have been extensively explored, but the results are inconsistent. Obesity is thought to affect bone health through a variety of mechanisms, including body weight, fat volume, bone formation/resorption, proinflammatory cytokines together with bone marrow microenvironment. In this review, we will mainly describe the effects of adipokines secreted by white adipose tissue on bone cells, as well as the interaction between brown adipose tissue, bone marrow adipose tissue, and bone metabolism. Meanwhile, this review also reviews the evidence for the effects of adipose tissue and its distribution on bone mass and bone-related diseases, along with the correlation between different populations with obesity and bone health. And we describe changes in bone metabolism in patients with anorexia nervosa or type 2 diabetes. In summary, all of these findings show that the response of skeleton to obesity is complex and depends on diversified factors, such as mechanical loading, obesity type, the location of adipose tissue, gender, age, bone sites, and secreted cytokines, and that these factors may exert a primary function in bone health.

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Section: Elderly Patients With Obesitymentioning

confidence: 99%

Obesity and Bone Health: A Complex Link

Hou

et al. 2020

Front. Cell Dev. Biol.

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“…It has been reported that osteogenic exercise inhibits sclerostin and myostatin, but induces irisin 40 . However, our research has shown that running a marathon with the differences in altitude along the route induces an upregulation of sclerostin, with a steady increase observed 72 h post-run.…”

Section: Discussionmentioning

confidence: 99%

Effects of marathon race on selected myokines and sclerostin in middle-aged male amateur runners

Śliwicka¹,

Cisoń

Ziemba

et al. 2021

Sci Rep

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In recent years, there has been increasing interest in the homeostatic response to extreme exercises, especially in the integrated function of muscle and bone. The aim of this study was to evaluate the effects of a marathon race on selected myokines and sclerostin in 10 male recreational runners (mean age 41 ± 7.7 years). Body composition, bone mineral density (BMD), and the serum concentration of myostatin, irisin, sclerostin, osteoprotegerin (OPG), 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH), high-sensitivity interleukin-6 (hsIL-6), tumor necrosis factor α (TNFα), high-sensitivity C-reactive protein (hsCRP) and myoglobin, were determined 24 h before and 24 h and 72 h after a marathon race. Post-marathon increases were observed in the levels of myostatin (1.2-fold), OPG (1.5-fold), and PTH (1.3-fold), hsIL-6 (1.9-fold), myoglobin (4.1-fold), hsCRP (fivefold), TNFα (2.6-fold), after 24 h; and in myostatin (1.2-fold), irisin (1.1-fold), sclerostin (1.3-fold), OPG (1.3-fold), and PTH (1.4-fold), hsIL-6 (1.4-fold), TNFα (1.9-fold), after 72 h compared to the baseline level. The results show that in response to the marathon run, a complex network of endocrine interactions is initiated. Further research is needed to fully elucidate the long-term impact of prolonged high intensity exercise on the human body.

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“…Bone formation associated genes and signaling pathways were reported in bone biology and bone signaling pathways (21). The Wingless-related integration site (WNT), Hedgehog, TGF-β and osteoclast differentiation pathways were selected for further analysis based on previous studies on bone biology (22)(23)(24). Several genes which were regulated by miR-57-3p and miR-135a-3p co-participated in the aforementioned pathways (Table II).…”

Section: Aberrant Expression Of Mirnas In Osteoporotic Associatedmentioning

confidence: 99%

A validated miRNA signature for the diagnosis of osteoporosis related fractures using SVM algorithm classification

et al. 2020

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The aim of the present study was to develop a circulating microRNA expression signature for early prediction of osteoporotic fractures and to validate the results using Gene Expression Omnibus (GEO) datasets. The GSE70318 dataset was downloaded from GEO and used to build an osteoporotic fracture prediction model based on the receiver operating characteristic curve and support vector machine (SVM) classification index. The GSE74209 dataset was used as a validation dataset. Additionally, in vitro, alkaline phosphatase (ALP) activity was measured in the presence or absence of microRNA (miRNA/miR) treatments in human osteoblast cells. The expression of two selected genes was detected by western blotting. miR-188-3p, miR-942-3p, miR-576-3p and miR-135a-5p were differentially expressed between controls and osteoporotic patients with fractures. SVM classification using these four miRNAs provided better dichotomization. It was further confirmed that miR-576-3p and 135a-5p in the GSE74209 dataset could also significantly discriminate between the controls and fracture patients, the area under the curve of SVM2 was 0.9722 with 95% CI 0.8885-1.056. Further analysis indicated that the target genes of the two miRNAs participated in the Wingless-related integration site, Hedgehog and transforming growth factor-β signaling pathways and osteoclast differentiation. miR-576-3p and miR-135-5p transfection decreased ALP activity and ALP activity was increased in the presence of blocking antisense oligonucleotides. Western blotting indicated miR-576-3p and miR-135-5p decreased CSNK1A1L and LRP6 levels, respectively. In conclusion, two miRNA signatures were developed and validated for the prediction of osteoporotic fractures.

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Novel insights into the complex architecture of osteoporosis molecular genetics

Cited by 43 publications

References 186 publications

Obesity and Bone Health: A Complex Link

Obesity and Bone Health: A Complex Link

Effects of marathon race on selected myokines and sclerostin in middle-aged male amateur runners

A validated miRNA signature for the diagnosis of osteoporosis related fractures using SVM algorithm classification

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