TNF-α contributes to postmenopausal osteoporosis by synergistically promoting RANKL-induced osteoclast formation

Zha, Li; He, Li; Liang, Yijian; Qin, Hui; Yu, Bin; Chang, Lin‐Li; Xue, Li

doi:10.1016/j.biopha.2018.03.080

Cited by 105 publications

(68 citation statements)

References 20 publications

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“…That mechanism is probably dose dependent as it was shown that those IOs can induce liver and lung tissue inflammation while administered in high dosage [35]. Importantly, here we have found that IOs but only in combination with MF can significantly diminish expression of TNF-a, a cytokine which contributes to osteoporosis by triggering RANKLinduced osteoclast formation [36].…”

Section: Discussionsupporting

confidence: 53%

Iron oxides nanoparticles (IOs) exposed to magnetic field promote expression of osteogenic markers in osteoblasts through integrin alpha-3 (INTa-3) activation, inhibits osteoclasts activity and exerts anti-inflammatory action

Marycz¹,

Sobierajska²,

Roecken³

et al. 2020

J Nanobiotechnol

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Background: Prevalence of osteoporosis is rapidly growing and so searching for novel therapeutics. Yet, there is no drug on the market available to modulate osteoclasts and osteoblasts activity simultaneously. Thus in presented research we decided to fabricate nanocomposite able to: (i) enhance osteogenic differentiation of osteoblast, (i) reduce osteoclasts activity and (iii) reduce pro-inflammatory microenvironment. As a consequence we expect that fabricated material will be able to inhibit bone loss during osteoporosis. Results:The α-Fe 2 O 3 /γ-Fe 2 O 3 nanocomposite (IOs) was prepared using the modified sol-gel method. The structural properties, size, morphology and Zeta-potential of the particles were studied by means of XRPD (X-ray powder diffraction), SEM (Scanning Electron Microscopy), PALS and DLS techniques. The identification of both phases was checked by the use of Raman spectroscopy and Mössbauer measurement. Moreover, the magnetic properties of the obtained IOs nanoparticles were determined. Then biological properties of material were investigated with osteoblast (MC3T3), osteoclasts (4B12) and macrophages (RAW 264.7) in the presence or absence of magnetic field, using confocal microscope, RT-qPCR, western blot and cell analyser. Here we have found that fabricated IOs: (i) do not elicit immune response; (ii) reduce inflammation; (iii) enhance osteogenic differentiation of osteoblasts; (iv) modulates integrin expression and (v) triggers apoptosis of osteoclasts. Conclusion:Fabricated by our group α-Fe 2 O 3 /γ-Fe 2 O 3 nanocomposite may become an justified and effective therapeutic intervention during osteoporosis treatment.

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Section: Discussionsupporting

confidence: 53%

Iron oxides nanoparticles (IOs) exposed to magnetic field promote expression of osteogenic markers in osteoblasts through integrin alpha-3 (INTa-3) activation, inhibits osteoclasts activity and exerts anti-inflammatory action

Marycz¹,

Sobierajska²,

Roecken³

et al. 2020

J Nanobiotechnol

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“…Second, interleukin (IL)-1β and tumor necrosis factor (TNF)-α elevated by hepatic inflammation can activate osteoclasts [3]. Several studies have suggested that inflammatory cytokines including IL-1β and TNF-α cause bone loss by direct or indirect effects with complicated mechanisms [11][12][13][14]. Third, low serum IGF-1 levels can play a role in bone mass loss in chronic liver disease.…”

Section: Discussionmentioning

confidence: 99%

Severe hypocalcemia following denosumab treatment in a patient with secondary osteoporosis associated with primary sclerosing cholangitis

2019

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Primary sclerosing cholangitis (PSC) has been known as a cause of secondary osteoporosis, which often requires medication. Herein, we give the first report of a case of a 38-year-old man with fatigue and paralysis in both upper limbs who had been treated with denosumab for secondary osteoporosis associated with PSC. Since bisphosphonate (alendronate) was ineffective in our patient, the treatment was changed from alendronate to denosumab. Despite replacements with calcium and active vitamin D (alfacalcidol; 1-hydroxycholecalciferol), he developed severe hypocalcemia (albumin-adjusted serum calcium: 5.2 mg/dL) 2 weeks after the second administration of denosumab, which required immediate correction. After that, the corrected serum calcium levels were controlled within the normal range with 0.75 μg of eldecalcitol (1α,25-dihydroxy-2β-(3-hydroxypropyloxy)vitamin D3) and increased doses of calcium (1,500 mg daily) and phosphate (900 mg daily) without denosumab. Even though denosumab treatment had been terminated, the T score of the lumbar spine improved from-4.4 to-2.6 by 1 year after the second administration, possibly due to the amelioration of osteomalacia through the treatment with eldecalcitol and the higher doses of calcium and phosphate. This report indicates that denosumab can cause severe hypocalcemia in patients with osteoporosis associated with chronic diseases of the hepatobiliary system including PSC, in turn suggesting that the possibility of vitamin D deficiency or osteomalacia should be considered before administering treatments and that serum calcium levels should be closely monitored to detect life-threatening hypocalcemia in patients who have high risk factors for hypocalcemia.

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“…PtdIns(3,4,5)P3 can up-regulate the phosphorylation of Akt to phosphorylate numerous substrates regulating various cellular processes. PLEKHA1 is notably associated with the signaling pathway of PI3K/Akt, which plays an important role in osteoporosis [65,66]. Based on a mouse model, deletion of PtdIns (3,4,5)P 3 in the brain results in impaired bone mass and mineralization [67] and down-regulated PtdIns(3,4,5)P 3 levels also affected osteoclast activity and BMD [68].…”

Section: Discussionmentioning

confidence: 99%

Identification of novel variants associated with osteoporosis, type 2 diabetes and potentially pleiotropic loci using pleiotropic cFDR method

Tan

Chen

et al. 2018

Bone

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TNF-α contributes to postmenopausal osteoporosis by synergistically promoting RANKL-induced osteoclast formation

Cited by 105 publications

References 20 publications

Iron oxides nanoparticles (IOs) exposed to magnetic field promote expression of osteogenic markers in osteoblasts through integrin alpha-3 (INTa-3) activation, inhibits osteoclasts activity and exerts anti-inflammatory action

Iron oxides nanoparticles (IOs) exposed to magnetic field promote expression of osteogenic markers in osteoblasts through integrin alpha-3 (INTa-3) activation, inhibits osteoclasts activity and exerts anti-inflammatory action

Severe hypocalcemia following denosumab treatment in a patient with secondary osteoporosis associated with primary sclerosing cholangitis

Identification of novel variants associated with osteoporosis, type 2 diabetes and potentially pleiotropic loci using pleiotropic cFDR method

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