Inhibitory effects of melatonin on titanium particle-induced inflammatory bone resorption and osteoclastogenesis via suppression of NF-κB signaling

Ping, Zichuan; Wang, Zhirong; Shi, Jiawei; Wang, Liangliang; Guo, Xiaobin; Zhou, Wei; Hu, Xuanyang; Wu, Xiexing; Liu, Yu; Wen, Zhang; Yang, Huilin; Xu, Yaozeng; Gu, Ye

doi:10.1016/j.actbio.2017.08.046

Cited by 90 publications

(78 citation statements)

References 36 publications

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“…After melatonin treatment, there was a statistically significant decrease in the gingival index, pocket depth, and salivary levels of RANKL and a significant rise in salivary values of osteoprotegrin, indicating that melatonin has a favorable effect in slowing osteoclastogenesis, improving the quality of alveolar bone, and preventing the progression of periodontal disease . Additionally, melatonin inhibits RANKL‐induced osteoclast differentiation, F‐actin ring formation, and osteoclastic resorption in a concentration‐dependent manner in vitro . Koyama et al found that pharmacologic doses of melatonin elevates bone mass by suppressing resorption through downregulation of the RANKL‐mediated formation and activation of osteoclasts.…”

Section: Mechanisms Underlying Melatonin's Action On Osteoporosismentioning

confidence: 99%

Melatonin: Another avenue for treating osteoporosis?

Tian

Jiang

et al. 2019

Journal of Pineal Research

106

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Melatonin is a signal molecule that modulates the biological circadian rhythms of vertebrates. Melatonin deficiency is thought to be associated with several disorders, including insomnia, cancer, and cardiovascular and neurodegenerative diseases. Accumulating evidence has also indicated that melatonin may be involved in the homeostasis of bone metabolism. Age‐related reductions in melatonin are considered to be critical factors in bone loss and osteoporosis with aging. Thus, serum melatonin levels might serve as a biomarker for the early detection and prevention of osteoporosis. Compared to conventional antiosteoporosis medicines, which primarily inhibit bone loss, melatonin both suppresses bone loss and promotes new bone formation. Mechanistically, by activating melatonin receptor 2 (MT2), melatonin upregulates the gene expression of alkaline phosphatase (ALP), bone morphogenetic protein 2 (BMP2), BMP6, osteocalcin, and osteoprotegerin to promote osteogenesis while inhibiting the receptor activator of NF‐kB ligand (RANKL) pathway to suppress osteolysis. In view of the distinct actions of melatonin on bone metabolism, we hypothesize that melatonin may be a novel remedy for the prevention and clinical treatment of osteoporosis.

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Section: Mechanisms Underlying Melatonin's Action On Osteoporosismentioning

confidence: 99%

Melatonin: Another avenue for treating osteoporosis?

Tian

Jiang

et al. 2019

Journal of Pineal Research

106

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“…A-C, BMMs were stimulated with M-CSF, RANKL, and 0, 1.25, 2.5 or 5 μM Arc. 8,9 In normal cells, NF-κB is retained in the cytoplasm through combining with the inhibitory IκB protein. D and E, BMMs were seeded onto hydroxyapatite-coated plate and treated with the indicated concentrations of Arc.…”

Section: Discussionmentioning

confidence: 99%

“…3,4 Generally, wear particle stimulates recruitment of macrophages, fibroblasts, osteoblasts, and osteoclasts, and stimulates these cells to produce and secrete various cytokines and chemokines. 8,9 Therefore, the NF-κB signaling pathway is very important to stimulate periprosthetic osteolysis. 7 Considering the importance of osteoclast in this osteolytic disease, therapeutic targeting of excessive osteoclast formation provides a logical method for the treatment or prevention of wear particle-induced osteolysis and pathological bone loss.…”

Section: Introductionmentioning

confidence: 99%

“…5,6 These factors can, directly and indirectly, initiate overexpression of receptor activator of nuclear factor κΒ ligand (RANKL) and suppression of osteoprotegerin in osteoblasts, and subsequently induce excessive osteoclast formation and bone resorption. 8,9 Actually, several agents targeting osteoclast differentiation have been studied over the last decade, including bisphosphonates, erythromycin, strontium ranelate, and denosumab (a RANKL inhibitor). Osteoclasts are multinucleated giant cells originated from monocytes/macrophage progenitors through differentiation process mainly regulated by two key factors, including RANKL and macrophage colony-stimulating factor (M-CSF).…”

Section: Introductionmentioning

confidence: 99%

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Arctigenin inhibits RANKL‐induced osteoclastogenesis and hydroxyapatite resorption in vitro and prevents titanium particle–induced bone loss in vivo

Wei

Liang

Wei

et al. 2018

J of Cellular Biochemistry

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Wear particle–induced bone resorption leads to prosthesis loosening, which is a major complication associated with total joint arthroplasty. Although the exact mechanism remains unclear, wear particle–induced extensive osteoclastogenesis plays a critical role in this process. Thus, a potential treatment of prosthetic loosening is focused on suppressing extensive osteoclast formation and bone resorption, which prevents wear particle–induced osteolysis. Arctigenin isolated from Arctium lappa has numerous beneficial pharmacologic effects, including anti‐inflammatory, antiviral, and anticancer activities. Here, we explored the potential impact of arctigenin on titanium (Ti) particle–induced osteolysis in vivo. Our data showed that arctigenin significantly suppressed Ti particle–induced osteolysis and prevented bone destruction compared with Ti group. In addition, the number of osteoclasts reduced after treatment with arctigenin in vivo, indicating osteoclastogenesis might be inhibited by arctigenin. Next, bone marrow–derived macrophages were used to examine osteoclast differentiation, bone resorption, and activation of osteoclast‐related signaling pathways. The results showed that arctigenin inhibited RANKL‐induced osteoclastogenesis without any cytotoxicity and suppressed osteoclastic marker genes expression and hydroxyapatite resorption activity in a dose‐dependent manner. Additionally, arctigenin suppressed receptor activator of nuclear factor κΒ (NF‐κB) ligand–induced NF‐κB activation, concomitant with retarded IκBɑ degradation and inhibition of p65 nuclear translocation, leading to impaired osteoclastogenesis. Collectively, our results suggest that arctigenin is a promising candidate for the treatment of osteoclast‐related osteolytic diseases caused by excessive osteoclast formation.

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“…6,7 Therefore, inhibiting the inflammatory response and reducing the release of proinflammatory cytokines are considered an effective strategy for preventing and treating wear debris-mediated periprosthetic osteolysis. 6,7 Therefore, inhibiting the inflammatory response and reducing the release of proinflammatory cytokines are considered an effective strategy for preventing and treating wear debris-mediated periprosthetic osteolysis.…”

Section: Introductionmentioning

confidence: 99%