Regulation of osteoclast differentiation by the redox-dependent modulation of nuclear import of transcription factors

Yj, Huh; Jm, Kim; Kim, Ho; Song, Hyohak; So, Hon‐Cheong; Lee, Sy; Sb, Kwon; Kim, Hyung Jun; Kim, Ho-Hyun; Sh, Lee; Choi, Yongwon; Sc, Chung; Dw, Jeong; Bm, Min

doi:10.1038/sj.cdd.4401793

Cited by 81 publications

(71 citation statements)

References 37 publications

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“…Recent evidences in a limited number of clinical studies have shown that ROS and/or antioxidant systems can be involved in the pathogenesis of bone loss (36)(37)(38)(39). In fact, oxidative stress activates the differentiation of preosteoclasts in osteoclasts and strengthens the bone resorption (18,40) (Figure 1). A significant increase in the number and activity of osteoclasts as well as in the tartrateresistant acid phosphatase level was observed when H2O2 was added to cultures of human marrow mononuclear cells (36).…”

Section: Oxidative Stress In Bone Remodelingmentioning

confidence: 99%

Oxidative stress in bone remodeling: role of antioxidants

Domazetovic

Marcucci

Iantomasi

et al. 2017

ccmbm

544

524

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SummaryROS are highly reactive molecules which consist of a number of diverse chemical species, including radical and non-radical oxygen species. Oxidative stress occurs as a result of an overproduction of ROS not balanced by an adequate level of antioxidants. The natural antioxidants are: thiol compounds among which GSH is the most representative, and non-thiol compounds such as polyphenols, vitamins and also various enzymes. Many diseases have been linked to oxidative stress including bone diseases among which one of the most important is the osteoporosis. The redox state changes are also related to the bone remodeling process which allows the continuous bone regeneration through the coordinated action of bone cells: osteoclasts, osteoblasts and osteocytes. Changes in ROS and/or antioxidant systems seem to be involved in the pathogenesis of bone loss. ROS induce the apoptosis of osteoblasts and osteocytes, and this favours osteoclastogenesis and inhibits the mineralization and osteogenesis. Excessive osteocyte apoptosis correlates with oxidative stress causing an imbalance in favor of osteoclastogenesis which leads to increased turnover of bone remodeling and bone loss. Antioxidants either directly or by counteracting the action of oxidants contribute to activate the differentiation of osteoblasts, mineralization process and the reduction of osteoclast activity. In fact, a marked decrease in plasma antioxidants was found in aged or osteoporotic women. Some evidence shows a link among nutrients, antioxidant intake and bone health. Recent data demonstrate the antioxidant properties of various nutrients and their influence on bone metabolism. Polyphenols and anthocyanins are the most abundant antioxidants in the diet, and nutritional approaches to antioxidant strategies, in animals or selected groups of patients with osteoporosis or inflammatory bone diseases, suggest the antioxidant use in anti-resorptive therapies for the treatment and prevention of bone loss.

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Section: Oxidative Stress In Bone Remodelingmentioning

confidence: 99%

Oxidative stress in bone remodeling: role of antioxidants

Domazetovic

Marcucci

Iantomasi

et al. 2017

ccmbm

544

524

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“…Redox status affects bone metabolism, including osteoclast differentiation (18). Thiol antioxidants are mediators of estrogen deficiency-induced bone loss.…”

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confidence: 99%

“…Oxidative stress, which results in changes in the redox status of cells, plays important roles in aging as well as in many diseases, including malignancies, diabetes, neurodegenerative diseases, atherosclerosis, ischemia, autoimmunity, and HIV infection (14,15) Free radicals also are involved in the pathogenesis of osteoporosis (6). Dietary antioxidants (18,25), levels of plasma antioxidants (5,24), and oxidative stress (4) have been all linked with bone density and the risk of hip fracture. At the cellular level, ROS have been found to stimulate osteoclastic bone resorption (22,23) and osteoclast differentiation (3,9), whereas free radical scavengers and antioxidants are inhibitory.…”

mentioning

confidence: 99%

PAMM: A Redox Regulatory Protein That Modulates Osteoclast Differentiation

Xu¹,

Morse

Silva

et al. 2010

Antioxidants & Redox Signaling

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The central role of reactive oxygen species (ROS) in osteoclast differentiation and in bone homeostasis prompted us to characterize the redox regulatory system of osteoclasts. In this report, we describe the expression and functional characterization of PAMM, a CXXC motif-containing peroxiredoxin 2-like protein expressed in bone marrow monocytes on stimulation with M-CSF and RANKL. Expression of wild-type (but not C to G mutants of the CXXC domain) PAMM in HEK293 cells results in an increased GSH=GSSG ratio, indicating a shift toward a more reduced environment. Expression of PAMM in RAW264.7 monocytes protected cells from hydrogen peroxide-induced oxidative stress, indicating that PAMM regulates cellular redox status. RANKL stimulation of RAW 264.7 cells caused a decrease in the GSH=GSSG ratio (reflecting a complementary increase in ROS). In addition, RANKL-induced osteoclast formation requires phosphorylation and translocation of NF-kB and c-Jun. In stably transfected RAW 264.7 cells, PAMM overexpression prevented the reduction of GSH=GSSG induced by RANKL. Concurrently, PAMM expression completely abolished RANKL-induced p100 NF-kB and c-Jun activation, as well as osteoclast formation. We conclude that PAMM is a redox regulatory protein that modulates osteoclast differentiation in vitro. PAMM expression may affect bone resorption in vivo and help to maintain bone mass. Antioxid. Redox Signal. 13, 27-37.

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“…Conversely, suppression of ROS during osteoclast differentiation inhibits ROS production, activation of MAP kinase, and osteoclast differentiation in BMMs (7,23). However, the total GSH content decreased during osteoclast differentiation; thus, GSH depletion by BSO, a specific inhibitor of GSH synthesis, inhibits osteoclastogenesis and bone pit formation in BMMs, suggesting the involvement of the GSH system in the process of osteoclastogenesis (9,10). In fact, we analyzed intracellular ROS in the condition of overexpression and depletion of Glrx2b in BMMs (Supplementary Fig.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, GSH depletion by L-buthionine-(S,R)-sulfoximine (BSO), a specific inhibitor of GSH synthesis, inhibits osteoclastogenesis and bone pit formation by blocking nuclear importation of NF-κB and AP-1 in RANKL-mediated signaling in RAW 264.7 cells (10). Furthermore, antioxidant enzymes regulating ROS have been shown to http://bmbreports.org Fig.…”

Section: Introductionmentioning

confidence: 99%