Protocatechuic Acid Attenuates Osteoclastogenesis by Downregulating JNK/c‐Fos/NFATc1 Signaling and Prevents Inflammatory Bone Loss in Mice

Park, Sun-Hyang; Kim, Ju‐Young; Cheon, Yoon‐Hee; Baek, Jong Min; Ahn, Sung‐Jun; Yoon, Kwon‐Ha; Lee, Myeung Su; Oh, Jae‐Min

doi:10.1002/ptr.5565

Cited by 32 publications

(26 citation statements)

References 31 publications

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“…In vivo, PCA was shown to have a protective effect against LPS-induced bone loss. PCA was also found to downregulate the expression of osteoclastogenesis-related genes, including DC-STAMP and b3-integrin (Park et al, 2016b).…”

Section: Anti-diabetes Activitymentioning

confidence: 93%

Sinapinic and protocatechuic acids found in rapeseed: isolation, characterisation and potential benefits for human health as functional food ingredients

Quinn

Gray

Meaney³

et al. 2017

Irish Journal of Agricultural and Food Research

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Rapeseed is one of the world’s major oilseeds, and rapeseed oil is produced by pressing of the seeds. This process results in the production of a low-economic-value by-product, rapeseed meal, which is commonly used as animal feed. Rapeseed meal is rich in bioactive phenolic compounds, including sinapinic acid (SA) and protocatechuic acid (PCA). Isolation of these bioactive compounds from a by-product of rapeseed oil production is largely in agreement with the current concept of the circular economy and total utilisation of crop harvest using a biorefinery approach. In this review, current information concerning traditional and novel methods to isolate phenolic compounds – including SA and PCA – from rapeseed meal, along with in vitro and in vivo studies concerning the bioactivity of SA and PCA and their associated health effects, is collated. These health effects include anti-inflammatory, anti-cancer, anti-diabetes activities, along with histone deacetylase inhibition and protective cardiovascular, neurological and hepatic effects. The traditional extraction methods include use of solvents and/or enzymes. However, a need for simpler, more efficient methodologies has led to the development of novel extraction processes, including microwave-assisted, ultrasound-assisted, pulsed electric field and high-voltage electrical discharge extraction processes.

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Section: Anti-diabetes Activitymentioning

confidence: 93%

Sinapinic and protocatechuic acids found in rapeseed: isolation, characterisation and potential benefits for human health as functional food ingredients

Quinn

Gray

Meaney³

et al. 2017

Irish Journal of Agricultural and Food Research

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show abstract

“…In addition, the RANKL-mediated signaling pathways including mitogen-activated protein kinases, nuclear factor κ B, and cyclooygenase-2 could be attenuated by PCA treatment [ 21 ]. Park et al have shown that PCA inhibits RANKL-induced osteoclast differentiation in mouse bone marrow macrophages and lipopolysaccharide-induced inflammatory bone loss in mice [ 24 ]. In contrast, Rivera-Piza et al suggested in 2017 that PCA might enhance osteogenesis in C3H10T1/2 and 3T3-L1 cells [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Protocatechuic Acid Attenuates Trabecular Bone Loss in Ovariectomized Mice

Jang

Song

Kwon

et al. 2018

Oxidative Medicine and Cellular Longevity

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Primary osteoporosis is a disease related to excessive bone resorption due to estrogen insufficiency that occurs postmenopause. Protocatechuic acid (PCA), or 3,4-dihydroxybenzoic acid, is a common compound present in numerous plants. Although numerous biological activities of PCA have been identified, its antiosteoporotic function has not been well established. In this study, the antiosteoporotic activity of PCA supplementation was determined in ovariectomized (OVX) female ICR mice at 12 weeks after OVX. The biomechanical properties of a bone were evaluated by microcomputed tomography. The signaling molecules associated with osteoclast differentiation were determined in bone marrow cells through immunoblot or RT-PCR. Oral supplementation with PCA (20 mg/kg/day) significantly ameliorated the OVX-mediated stimulation of osteoclast activity based on decreases in serum levels of receptor activator of nuclear factor κB ligand (RANKL), osteocalcin, and bone alkaline phosphatase and increase in serum osteoprotegerin (each group, n = 6; p < 0.05). In addition, the OVX-induced decreases in mRNA expression levels of cathepsin K, calcitonin receptor, nuclear factor of activated T cell cytoplasmic 1 (NFATc1), and tumor necrosis factor (TNF) receptor-associated factor-6 (TRAF6) in bone marrow cells were significantly attenuated (each group, n = 6; p < 0.05). Finally, the loss of trabecular bone and changes in biomechanical properties of a bone were significantly improved by supplementation with 20 mg/kg PCA (each group, n = 6; p < 0.05). Collectively, our results show that PCA supplement suppressed trabecular bone loss in OVX mice and therefore might be an effective alternative approach for preventing the progression of postmenopausal osteoporosis.

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“…In the present study, we have demonstrated for the first time that We attempted to define the underlying mechanism for DAP's antiosteoclastogenic effect in vitro by exploring the effects of DAP (Deepak, Kruger, & Coetzee, 2016;Miyazaki et al, 2000;Park et al, 2016).…”

Section: Dap Affects Rankl-induced Erk Phosphorylation and Nfatc1 Amentioning

confidence: 90%

Daphnetin attenuates LPS‐induced osteolysis and RANKL mediated osteoclastogenesis through suppression of ERK and NFATc1 pathways

et al. 2019

Journal Cellular Physiology

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Aseptic prosthetic loosening and periprosthetic infection resulting in inflammatory osteolysis is a leading complication of total joint arthroplasty (TJA). Excessive bone destruction around the bone and prosthesis interface plays a key role in the loosening prostheses leading to revision surgery. The bacterial endotoxins or implant‐derived wear particles‐induced inflammatory response is the major cause of the elevated osteoclast formation and activity. Thus, agents or compounds that can attenuate the inflammatory response and/or inhibit the elevated osteoclastogenesis and excessive bone resorption would provide a promising therapeutic avenue to prevent aseptic prosthetic loosening in TJA. Daphnetin (DAP), a natural coumarin derivative, is clinically used in Traditional Chinese Medicine for the treatment of rheumatoid arthritis due to its anti‐inflammatory properties. In this study, we report for the first time that DAP could protect against lipopolysaccharide‐induced inflammatory bone destruction in a murine calvarial osteolysis model in vivo. This protective effect of DAP can in part be attributed to its direct inhibitory effect on RANKL‐induced osteoclast differentiation, fusion, and bone resorption in vitro. Biochemical analysis found that DAP inhibited the activation of the ERK and NFATc1 signaling cascades. Collectively, our findings suggest that DAP as a natural compound has potential for the treatment of inflammatory osteolysis.

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Protocatechuic Acid Attenuates Osteoclastogenesis by Downregulating JNK/c‐Fos/NFATc1 Signaling and Prevents Inflammatory Bone Loss in Mice

Cited by 32 publications

References 31 publications

Sinapinic and protocatechuic acids found in rapeseed: isolation, characterisation and potential benefits for human health as functional food ingredients

Sinapinic and protocatechuic acids found in rapeseed: isolation, characterisation and potential benefits for human health as functional food ingredients

Protocatechuic Acid Attenuates Trabecular Bone Loss in Ovariectomized Mice

Daphnetin attenuates LPS‐induced osteolysis and RANKL mediated osteoclastogenesis through suppression of ERK and NFATc1 pathways

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