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Bone Metabolism and Plant-Derived Pharmaceuticals

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A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Phytochemicals and Human Health".

Deadline for manuscript submissions: closed (20 February 2024) | Viewed by 8583

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Special Issue Editor

Dr. Simon Fox

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Guest Editor

School of Biomedical Sciences, Faculty of Health: Medicine, Dentistry and Human Health, University of Plymouth, Plymouth, UK
Interests: skeletal metabolism; bone cell activity; osteoporosis; secondary bone cancers; phytochemicals; medicinal plants

Special Issue Information

Dear Colleagues,

Bone homeostasis is regulated by a balance between osteoblastic bone formation and osteoclast bone resorption. Disruption of this balance is a hallmark of skeletal disorders such as osteoporosis, bone cancer and arthritis, which in aging populations represent major healthcare challenges.

Numerous epidemiological studies have linked diet and skeletal health. In particular, plant-rich diets or supplements have been suggested to improve skeletal metabolism and bone health. Plants contain a multitude of metabolically active compounds that could affect bone cell activity, but understanding of the nature of these compounds and their impact on bone metabolism is incomplete.

This Special Issue, “Bone Metabolism and Plant-Derived Pharmaceuticals”, welcomes original articles, reviews, or meta-analyses exploring the impact of plant-derived compounds on bone cell activity, turnover and skeletal health and disease, with special interest in underlying cellular and molecular mechanisms. This may help to identify novel plant-derived pharmaceuticals or inform dietary or lifestyle recommendations.

Dr. Simon Fox
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nutrients is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

osteoblastic formation
osteoclastic resorption
remodelling
osteoporosis
bone cancer
plant-derived compounds

Published Papers (5 papers)

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Research

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23 pages, 2541 KiB

Open AccessArticle

Genistein Supplementation and Bone Health in Breast Cancer in Rats

by Dorota Skrajnowska, Wojciech Bielecki, Arkadiusz Szterk, Karol Ofiara and Barbara Bobrowska-Korczak

Nutrients 2024, 16(6), 912; https://doi.org/10.3390/nu16060912 - 21 Mar 2024

Viewed by 809

Abstract

The aim of our study was to analyse the effect of supplementation with various forms of genistein (nano-, micro-, and macro-) on the mineral status of rat femurs in conditions of DMBA-induced mammary gland neoplasia. Thirty-two 30-day-old Sprague Dawley rats were used in the study. The rats were divided into four experimental groups: a control group (without supplementation) and groups supplemented with nanosized (92 ± 41 nm), microsized (587 ± 83 nm), and macrosized genistein. Micromorphometric and histological examination of the rat femurs were performed, as well as analysis of the weight and mineral composition (17 elements). Quadrupole ICP-MS was used for analysis of all trace elements. Supplementation with genistein (nano-, micro-, and macro-) was shown to cause changes in the mineral composition of the bones. In the rats receiving nanogenistein, disintegration of the bone tissue was observed. The femurs of these animals had higher content of calcium (by nearly 300%) and potassium (by 25%) than the other groups, while the level of magnesium was about 22% lower. In the case of microelements, there were increases in copper (by 67%), boron (48%), manganese (13%), and nickel (100%), and a 16% decrease in strontium compared to the bones of rats without genistein supplementation. Changes in micromorphometric parameters, resulting in increased bone fragility, were observed. Administration of genistein was found to have an effect on the amount of trace elements in the bone tissue of rats with breast cancer. Full article

(This article belongs to the Special Issue Bone Metabolism and Plant-Derived Pharmaceuticals)

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18 pages, 7137 KiB

Open AccessArticle

Peonidin-3-O-glucoside and Resveratrol Increase the Viability of Cultured Human hFOB Osteoblasts and Alter the Expression of Genes Associated with Apoptosis, Osteoblast Differentiation and Osteoclastogenesis

by Keila C. Ostos Mendoza, Karen D. Garay Buenrostro, Pinal N. Kanabar, Mark Maienschein-Cline, Nina S. Los, Zarema Arbieva, Nishikant A. Raut, Temitope O. Lawal, Alice M. López, Paulina Cabada-Aguirre, Diego A. Luna-Vital and Gail B. Mahady

Nutrients 2023, 15(14), 3233; https://doi.org/10.3390/nu15143233 - 21 Jul 2023

Viewed by 1068

Abstract

High-throughput RNA-sequencing can determine the impact of nutrients and their combinations on gene transcription levels in osteocytes, and clarify the biological pathways associated with their impact on bone tissues. Previously, we reported that resveratrol (RES) and peonidin-3-O-glucoside (POG) increased osteoblastogenesis, as well as reduced osteoclastogenesis in transgenic teleost fish models. Here, we perform whole-genome transcriptomic profiling of osteoblasts treated with POG or RES to provide a comprehensive understanding of alterations in gene expression and the molecular mechanisms involved. Cultured human fetal osteoblastic hFOB 1.19 cells were treated with the test compounds, and then RNA was used to prepare RNA-seq libraries, that were sequenced using a NovaSeq 6000. Treatment with POG or RES increased osteoblast proliferation and reduced apoptosis. Transcriptomic profiling showed that of the 29,762 genes investigated, 3177 were differentially expressed (1481 upregulated, 1696 downregulated, FDR ≤ 0.05) in POG-treated osteoblasts. In the RES-treated osteoblasts, 2288 genes were differentially expressed (DGEs, 1068 upregulated, 1220 downregulated, FDR ≤ 0.05). Ingenuity^® Pathway Analysis (IPA) of DGEs from RES or POG-treated osteoblasts revealed significant downregulation of the apoptosis, osteoarthritis and HIF1α canonical pathways, and a significant reduction in Rankl mRNA expression. The data suggest that RES and POG have both anabolic and anticlastogenic effects. Full article

(This article belongs to the Special Issue Bone Metabolism and Plant-Derived Pharmaceuticals)

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15 pages, 5865 KiB

Open AccessArticle

Plum-Derived Exosome-like Nanovesicles Induce Differentiation of Osteoblasts and Reduction of Osteoclast Activation

by Yu-Seong Park, Hyun-Woo Kim, Jin-Hyeon Hwang, Jung-Young Eom, Dong-Ha Kim, Jinho Park, Hyun-Jin Tae, Seunghoon Lee, Jae-Gyu Yoo, Jee-In Kim, Jae-Hwan Lim, In-Sook Kwun, Moon-Chang Baek, Young-Eun Cho and Do-Kyun Kim

Nutrients 2023, 15(9), 2107; https://doi.org/10.3390/nu15092107 - 27 Apr 2023

Cited by 3 | Viewed by 1875

Abstract

Osteoblasts and osteoclasts play crucial roles in bone formation and bone resorption. We found that plum-derived exosome-like nanovesicles (PENVs) suppressed osteoclast activation and modulated osteoblast differentiation. PENVs increased the proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells and osteoblasts from mouse bone marrow cultures. Notably, PENVs elevated the expression of osteoblastic transcription factors and osteoblast differentiation marker proteins in MC3T3-E1 cells. Higher levels of phosphorylated BMP-2, p38, JNK, and smad1 proteins were detected in PENV-treated MC3T3-E1 cells. Additionally, the number of TRAP-positive cells was significantly decreased in PENV-treated osteoclasts isolated from osteoblasts from mouse bone marrow cultures. Importantly, osteoclastogenesis of marker proteins such as PPAR-gamma, NFATc1, and c-Fos were suppressed by treatment with PENVs (50 μg/mL). Taken together, these results demonstrate that PENVs can be used as therapeutic targets for treating bone-related diseases by improving osteoblast differentiation and inhibiting osteoclast activation for the first time. Full article

(This article belongs to the Special Issue Bone Metabolism and Plant-Derived Pharmaceuticals)

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13 pages, 3312 KiB

Open AccessArticle

Effects of 4′-Demethylnobiletin and 4′-Demethyltangeretin on Osteoclast Differentiation In Vitro and in a Mouse Model of Estrogen-Deficient Bone Resorption

by Michiko Hirata, Tsukasa Tominari, Ryota Ichimaru, Naruhiko Takiguchi, Yuki Tanaka, Masaru Takatoya, Daichi Arai, Shosei Yoshinouchi, Chisato Miyaura, Chiho Matsumoto, Sihui Ma, Katsuhiko Suzuki, Florian M. W. Grundler and Masaki Inada

Nutrients 2023, 15(6), 1403; https://doi.org/10.3390/nu15061403 - 14 Mar 2023

Viewed by 1372

Abstract

Citrus nobiletin (NOB) and tangeretin (TAN) show protective effects against disease-related bone destruction. We achieved demethylation of NOB and TAN into 4′-demethylnobiletin (4′-DN) and 4′-demethyltangeretin (4′-DT) using enzyme-manufacturing methods. In this study, we examined the effects of 4′-DN and 4′-DT on in vitro osteoclast differentiation, and on in vivo osteoporotic bone loss in ovariectomized (OVX) mice. 4′-DN and 4′-DT clearly suppressed the osteoclast differentiation induced by interleukin IL-1 or RANKL treatment. 4′-DN and 4′-DT treatments resulted in higher inhibitory activity in osteoclasts in comparison to NOB or TAN treatments. RANKL induced the increased expression of its marker genes and the degradation of IκBα in osteoclasts, while these were perfectly attenuated by the treatment with 4′-MIX: a mixture of 4′-DN and 4′-DT. In an in silico docking analysis, 4′-DN and 4′-DT directly bound to the ATP-binding pocket of IKKβ for functional inhibition. Finally, the intraperitoneal administration of 4′-MIX significantly protected against bone loss in OVX mice. In conclusion, 4′-DN, 4′-DT and 4′-MIX inhibited the differentiation and function of bone-resorbing osteoclasts via suppression of the NF-κB pathway. Novel 4′-DN, 4′-DT and 4′-MIX are candidates for maintaining bone health, which may be applied in the prevention of metabolic bone diseases, such as osteoporosis. Full article

(This article belongs to the Special Issue Bone Metabolism and Plant-Derived Pharmaceuticals)

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Review

Jump to: Research

33 pages, 2803 KiB

Open AccessReview

Bioactivity, Molecular Mechanism, and Targeted Delivery of Flavonoids for Bone Loss

by Ashish Ranjan Sharma, Yeon-Hee Lee, Altanzul Bat-Ulzii, Srijan Chatterjee, Manojit Bhattacharya, Chiranjib Chakraborty and Sang-Soo Lee

Nutrients 2023, 15(4), 919; https://doi.org/10.3390/nu15040919 - 12 Feb 2023

Cited by 3 | Viewed by 2944

Abstract

Skeletal disabilities are a prominent burden on the present population with an increasing life span. Advances in osteopathy have provided various medical support for bone-related diseases, including pharmacological and prosthesis interventions. However, therapeutics and post-surgery complications are often reported due to side effects associated with modern-day therapies. Thus, therapies utilizing natural means with fewer toxic or other side effects are the key to acceptable interventions. Flavonoids constitute a class of bioactive compounds found in dietary supplements, and their pharmacological attributes have been well appreciated. Recently, flavonoids’ role is gaining renowned interest for its effect on bone remodeling. A wide range of flavonoids has been found to play a pivotal role in the major bone signaling pathways, such as wingless-related integration site (Wnt)/β-catenin, bone morphogenetic protein (BMP)/transforming growth factor (TGF)-β, mitogen-activated protein kinase (MAPK), etc. However, the reduced bioavailability and the absorption of flavonoids are the major limitations inhibiting their use against bone-related complications. Recent utilization of nanotechnological approaches and other delivery methods (biomaterial scaffolds, micelles) to target and control release can enhance the absorption and bioavailability of flavonoids. Thus, we have tried to recapitulate the understanding of the role of flavonoids in regulating signaling mechanisms affecting bone remodeling and various delivery methods utilized to enhance their therapeutical potential in treating bone loss. Full article

(This article belongs to the Special Issue Bone Metabolism and Plant-Derived Pharmaceuticals)

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