Screening of osteoprotegerin-related feature genes in osteoporosis and functional analysis with DNA microarray

Wu, Xiaoming; Shu-zhang, Guo; Shen, Guanghao; Ma, Xing; Tang, Chi; Xie, Kangning; Liu, Juan; Guo, Wei; Yan, Yishu; Luo, Erping

doi:10.1186/2047-783x-18-15

Cited by 5 publications

(4 citation statements)

References 29 publications

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“…In vivo OPG binds RANKL and blocks its interaction with RANK [53]. The binding may be inhibited by collagen 1α1 [54], while TNF-α enhances the concentration of both proteins [55]. In addition, sclerostin (SOST) and the bone morphogenic protein 2 (BMP2) have an influence on the RANKL/OPG system.…”

Section: Resultsmentioning

confidence: 99%

Changes in Human Foetal Osteoblasts Exposed to the Random Positioning Machine and Bone Construct Tissue Engineering

Mann

Grimm

Corydon

et al. 2019

IJMS

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Human cells, when exposed to both real and simulated microgravity (s-µg), form 3D tissue constructs mirroring in vivo architectures (e.g., cartilage, intima constructs, cancer spheroids and others). In this study, we exposed human foetal osteoblast (hFOB 1.19) cells to a Random Positioning Machine (RPM) for 7 days and 14 days, with the purpose of investigating the effects of s-µg on biological processes and to engineer 3D bone constructs. RPM exposure of the hFOB 1.19 cells induces alterations in the cytoskeleton, cell adhesion, extra cellular matrix (ECM) and the 3D multicellular spheroid (MCS) formation. In addition, after 7 days, it influences the morphological appearance of these cells, as it forces adherent cells to detach from the surface and assemble into 3D structures. The RPM-exposed hFOB 1.19 cells exhibited a differential gene expression of the following genes: transforming growth factor beta 1 (TGFB1, bone morphogenic protein 2 (BMP2), SRY-Box 9 (SOX9), actin beta (ACTB), beta tubulin (TUBB), vimentin (VIM), laminin subunit alpha 1 (LAMA1), collagen type 1 alpha 1 (COL1A1), phosphoprotein 1 (SPP1) and fibronectin 1 (FN1). RPM exposure also induced a significantly altered release of the cytokines and bone biomarkers sclerostin (SOST), osteocalcin (OC), osteoprotegerin (OPG), osteopontin (OPN), interleukin 1 beta (IL-1β) and tumour necrosis factor 1 alpha (TNF-1α). After the two-week RPM exposure, the spheroids presented a bone-specific morphology. In conclusion, culturing cells in s-µg under gravitational unloading represents a novel technology for tissue-engineering of bone constructs and it can be used for investigating the mechanisms behind spaceflight-related bone loss as well as bone diseases such as osteonecrosis or bone injuries.

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Section: Resultsmentioning

confidence: 99%

Changes in Human Foetal Osteoblasts Exposed to the Random Positioning Machine and Bone Construct Tissue Engineering

Mann

Grimm

Corydon

et al. 2019

IJMS

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“…BMD is under strong genetic control, where as much as 60% of the variance in BMD has been attributed to genetic factors (Chen et al, 2005). In addition, the incidence of osteoporosis in elderly people and post-menopausal women is rising as the population ages, adding to the societal problems of health (Wu et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…According to the World Health Organization, 13-18% of women and 3-6% of men aged more than 50 years suffer from osteoporosis worldwide (Rosa, 2015), affecting 200 million people (Wu et al, 2013). In Brazil, approximately 10 million people have osteoporosis (http://portalsaude.saude.gov.br).…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in CYP17, COMT, and ESR1 genes in women after menopause and association with bone mineral density

Gonçalves¹,

Almeida²,

Camargo-Kosugi³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. In this study, we evaluated genetic factors related to the mineral density during post-menopause. We evaluated 110 women in the first 5 years post-menopause, without previous hormone replacement therapy. Cytochrome P450 17 (CYP17) (rs743572), catechol-O-methyl transferase (COMT) (rs4680), and estrogen receptor 1 (ESR1) (rs9322331) were examined for the presence of polymorphisms. Clinical data were collected by anamnesis; all patients had the osseous densitometry examined using a lunar instrument to determine mineral osseous densitometry in the lumbar column (L2-L4). CYP17, COMT, and ESR1 genotyping was carried out by polymerase chain reaction with DNA collected from buccal swabs. The average age was 51.96 years. The average weights of the patients in control and osteopenia groups were 70.25 ± 12.00 and 62.45 ± 11.64, respectively (P = 0.001) and body mass index (P = 0.006; control: 29.43 ± 5.25; osteopenia: 26.72 ± 4.57). Related to CYP17 polymorphisms, 28.18% of women were TT (wild-type homozygous), 60% 15802-15810 (2015) were TC (heterozygous), and 11.82% were CC (mutated homozygous). Related to COMT polymorphisms, 53.64% of women were GG (wild-type homozygous), 37.27% were GA (heterozygous), and 9.09% were AA (mutated homozygous). Related to ESR1, 53.64% of women were CC (wildtype homozygous), 40.91% were CT (heterozygous), and 5.45% were TT (mutated homozygous). The ESR1 variant allele was significantly higher in the osteopenia group when compared with women in the normal group (P = 0.02). ESR1 may be associated with low mineral osseous densitometry, while CYP17 and COMT gene polymorphisms were not associated with mineral osseous densitometry.

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“…The risk factors consist of age, gender, race, and other factors which may disturb the balance between bone loss and bone formation (e.g., lack of oestrogen, serum calcium level alteration, prolonged use of glucocorticoids). Currently, drugs are the main treatment for osteoporosis, however, the curative effect is limited, accompanied by side effects and high costs (Wu et al, 2013). Thus, huge efforts have been devoted to explore novel and effective targets for the treatment of osteoporosis.…”

Section: Introductionmentioning

confidence: 99%

Alteration of gut microbiota in elderly postmenopausal women with osteoporosis

et al. 2020

Preprint

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Osteoporosis is a common bone disorder worldwide and causes bone fragility and fracture. Gut microbiota colonizes the gastrointestinal tract, and is associated with bone metabolism and osteoporosis. In our study, the alteration of gut microbiota in osteoporosis and its effects on bone metabolism were investigated. A total of 36 elderly postmenopausal osteoporotic women and 12 healthy controls were recruited, and their fecal samples were collected for 16S rRNA gene sequencing of gut microbiota on Illumina MiSeq platform. The venous blood and urine samples were also collected to determine the biochemical indexes. There was no obvious difference in Alpha diversity in the experiment group and control group, while differential Beta diversity was observed. The Partial Least Squares Discriminant Analysis (PLS-DA) model and variable importance in projection (VIP) scores showed that the osteoporotic women and healthy controls had different genera of Erysipelotrichaceae , Rothia , and Eubacterium . The metabolic function prediction of gut microbiota indicated that the experiment group had 634 unique functional categories, while the control group had 13 unique functional categories. The biochemical measurement revealed that the osteoclast activity indexes including urine N-terminal telopeptides of type I collagen (NTX), serum NTX, and serum C-terminal telopeptides of type I collagen (CTX) in the experiment group were higher than those in the control group, indicating that the osteoclast activity in osteoporotic women was increased. In addition, the correlation analysis of microbial metabolism with phenotypes showed the pathways in the significant modules of magenta, red, pink, and yellow were positively correlated with urine phosphate, urine creatinine, urine creatinine, serum calcium and other biochemical indexes. Collectively, our study identified the different genera between postmenopausal osteoporotic women and healthy controls, which might be potential targets for the treatment of osteoporosis.

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Screening of osteoprotegerin-related feature genes in osteoporosis and functional analysis with DNA microarray

Cited by 5 publications

References 29 publications

Changes in Human Foetal Osteoblasts Exposed to the Random Positioning Machine and Bone Construct Tissue Engineering

Changes in Human Foetal Osteoblasts Exposed to the Random Positioning Machine and Bone Construct Tissue Engineering

Polymorphisms in CYP17, COMT, and ESR1 genes in women after menopause and association with bone mineral density

Alteration of gut microbiota in elderly postmenopausal women with osteoporosis

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