Melatonin, bone regulation and the ubiquitin-proteasome connection: A review

Vriend, Jerry; Reíter, Russel J.

doi:10.1016/j.lfs.2015.12.031

Cited by 57 publications

(46 citation statements)

References 136 publications

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“…The ubiquitination process is reversible through the action of deubiquitinases that remove ubiquitin marks (Komander et al , ). Significant progress has been made in understanding the molecular regulation of MSC differentiation by ubiquitin ligases (Severe et al , ; Vriend & Reiter, ). For example, the E3 enzyme Smurf1 mediates the degradation of RUNX2, MEKK2, and JunB, resulting in inhibition of osteoblast differentiation and bone formation (Zhao et al , , ; Yamashita et al , ).…”

Section: Introductionmentioning

confidence: 99%

Ubiquitin‐specific protease USP 34 controls osteogenic differentiation and bone formation by regulating BMP 2 signaling

et al. 2018

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The osteogenic differentiation of mesenchymal stem cells (MSCs) is governed by multiple mechanisms. Growing evidence indicates that ubiquitin-dependent protein degradation is critical for the differentiation of MSCs and bone formation; however, the function of ubiquitin-specific proteases, the largest subfamily of deubiquitylases, remains unclear. Here, we identify USP34 as a previously unknown regulator of osteogenesis. The expression of USP34 in human MSCs increases after osteogenic induction while depletion of USP34 inhibits osteogenic differentiation. Conditional knockout of Usp34 from MSCs or pre-osteoblasts leads to low bone mass in mice. Deletion of Usp34 also blunts BMP2-induced responses and impairs bone regeneration. Mechanically, we demonstrate that USP34 stabilizes both Smad1 and RUNX2 and that depletion of Smurf1 restores the osteogenic potential of Usp34-deficient MSCs Taken together, our data indicate that USP34 is required for osteogenic differentiation and bone formation.

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Section: Introductionmentioning

confidence: 99%

Ubiquitin‐specific protease USP 34 controls osteogenic differentiation and bone formation by regulating BMP 2 signaling

et al. 2018

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“…This study signals an increased risk of fracture after exposure to melatonin and needs to be replicated before any conclusion can be made to avoid melatonin. Melatonin is believed to have positive effects on bone by stimulating growth and inhibiting osteoclast activity . Thus, the mechanism by which melatonin might increase fracture risk is unclear.…”

Section: Resultsmentioning

confidence: 99%

Recent Literature Update on Medication Risk in Older Adults, 2015–2016

Koronkowski

Semla

Schmader

et al. 2017

J American Geriatrics Society

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Medications can pose considerable risk in older adults. This article annotates four articles addressing this concern from 2016. The first provides national data on the use of specific prescription, over-the-counter and dietary supplements in older adults and their change over time. The second discusses the opportunity of deprescribing ineffective/unnecessary stool softeners (i.e., docusate) routinely given to older hospital patients. The third national study examines common adverse drug events in older emergency room patients. Finally, a study published demonstrating a potential association between melatonin and fractures is discussed. This manuscript is intended to provide a narrative review of key publications in medication safety for clinicians and researchers committed to improving medication safety in older adults.

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“…The interaction between melatonin and the ubiquitin-proteasome system has been shown in mitochondria, brown fat, and oxidative stress 45 . Moreover, the suppressive effect of melatonin on ubiquitin-proteasome-mediated protein degradation regulates various osteoblastic markers and maintains a balance between bone formation and resorption 46 . With regard to the mechanisms underlying the regulation of Osterix expression by melatonin, we considered the possibility that this may be mediated via inhibition of the ubiquitin-proteasome degradation pathway.…”

Section: Discussionmentioning

confidence: 99%

Melatonin promotes osteoblast differentiation by regulating Osterix protein stability and expression

Han

Kim

et al. 2017

Sci Rep

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Although the biological role of melatonin in osteogenic differentiation has been suggested, the mechanism of osteoblast differentiation remains unclear. Thus, the present study investigated the underlying molecular mechanisms based on osteoblast-specific transcription factors. We found that melatonin enhanced BMP-4-induced osteogenic differentiation and increased the expression of osteogenic markers, especially Osterix, which is an essential transcription factor for the differentiation of preosteoblasts into mature osteoblasts in the late stage of osteoblast differentiation. Melatonin treatment increased the expression of Osterix during osteoblast differentiation and stabilized its expression by the inhibition of ubiquitin-proteasome-mediated degradation of Osterix, leading to up-regulated Osterix transcriptional activity on the osteogenic promoter and promoting alkaline phosphatase activity and bone mineralization. Furthermore, treatment with protein kinase A (PKA) inhibitor H89 and protein kinase C (PKC) inhibitor Go6976 blocked the melatonin-induced transcriptional activity and phosphorylation of Osterix, indicating that melatonin regulates Osterix expression via the PKA and PKC signaling pathways. Overall, these findings suggest that melatonin directly regulates the late stage of osteoblast differentiation by enhancing Osterix expression; this provides further evidence of melatonin as a potent agent for treating osteoporosis.

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Melatonin, bone regulation and the ubiquitin-proteasome connection: A review

Cited by 57 publications

References 136 publications

Ubiquitin‐specific protease USP 34 controls osteogenic differentiation and bone formation by regulating BMP 2 signaling

Ubiquitin‐specific protease USP 34 controls osteogenic differentiation and bone formation by regulating BMP 2 signaling

Recent Literature Update on Medication Risk in Older Adults, 2015–2016

Melatonin promotes osteoblast differentiation by regulating Osterix protein stability and expression

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