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The Role of Natural Compounds in Osteoblastic and Osteoclastic Cells

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (28 October 2022) | Viewed by 16891

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Special Issue Editors

Dr. Seon-Yong Jeong

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Guest Editor

Department of Medical Genetics, Ajou University School of Medicine, Suwon 16499, Republic of Korea
Interests: hergbal medicine; obesity; osteoporosis; menopausal symptoms; genetics and genomics; osteoarthritis
Special Issues, Collections and Topics in MDPI journals

Dr. Eunkuk Park

E-Mail Website
Co-Guest Editor

Department of Medical Genetics, Ajou University School of Medicine, Suwon 16499, Republic of Korea
Interests: osteoporosis; osteoarthritis; obesity; woman's menopause; cognitive impairment; phytomedicine; natural compounds; animal study
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Osteoporosis is an abnormal bone remodeling condition characterized by decreased bone density, which leads to high risks of fracture. It is a common disease caused by an imbalance between bone resorption by osteoclasts and bone formation by osteoblasts. Osteoporosis is a major concern in public health care, and causes severe consequences if left untreated. Although a few potent pharmacological therapies are available for the treatment of osteoporosis, most of these drugs have side effects. Herbal treatment for osteoporosis would be advantageous because natural plants have fewer side effects, making them more suitable for long‐term use. The preventive and therapeutic effects of phytochemicals, as potential alternative treatments for osteoporosis, have been reported.

We are particularly interested in manuscripts that describe the role of natural compounds in the bone remodeling process through the induction of osteoblast differentiation and/or the reduction of osteoclast differentiation. Therefore, this Special Issue will focus on the mode of action (molecular mechanisms) underlying the anti-osteoporotic effects of natural compounds. Original research articles, reviews, and letters on these topics are welcome in this Special Issue. It is also necessary to clarify the exact functional ingredient in the submitted research papers. We will not accept papers on mixed extraction.

Dr. Seon-Yong Jeong

Dr. Eunkuk Park
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

osteoporosis
fracture
herbal medicine
phytotherapy
natural compounds
molecular mechanism
bone remodeling
bone formation
bone resorption
osteoblasts
osteoclasts

Published Papers (6 papers)

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Research

Jump to: Review

12 pages, 5633 KiB

Open AccessArticle

Effects of Loganin on Bone Formation and Resorption In Vitro and In Vivo

by Chang-Gun Lee, Do-Wan Kim, Jeonghyun Kim, Laxmi Prasad Uprety, Kang-Il Oh, Shivani Singh, Jisu Yoo, Hyun-Seok Jin, Tae Hyun Choi, Eunkuk Park and Seon-Yong Jeong

Int. J. Mol. Sci. 2022, 23(22), 14128; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232214128 - 16 Nov 2022

Cited by 6 | Viewed by 1575

Abstract

Osteoporosis is a disease caused by impaired bone remodeling that is especially prevalent in elderly and postmenopausal women. Although numerous chemical agents have been developed to prevent osteoporosis, arguments remain regarding their side effects. Here, we demonstrated the effects of loganin, a single bioactive compound isolated from Cornus officinalis, on osteoblast and osteoclast differentiation in vitro and on ovariectomy (OVX)-induced osteoporosis in mice in vivo. Loganin treatment increased the differentiation of mouse preosteoblast cells into osteoblasts and suppressed osteoclast differentiation in primary monocytes by regulating the mRNA expression levels of differentiation markers. Similar results were obtained in an osteoblast–osteoclast co-culture system, which showed that loganin enhanced alkaline phosphatase (ALP) activity and reduced TRAP activity. In in vivo experiments, the oral administration of loganin prevented the OVX-induced loss of bone mineral density (BMD) and microstructure in mice and improved bone parameters. In addition, loganin significantly increased the serum OPG/RANKL ratio and promoted osteogenic activity during bone remodeling. Our findings suggest that loganin could be used as an alternative treatment to protect against osteoporosis. Full article

(This article belongs to the Special Issue The Role of Natural Compounds in Osteoblastic and Osteoclastic Cells)

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24 pages, 3474 KiB

Open AccessArticle

Antioxidative and Anti-Inflammatory Activities of Chrysin and Naringenin in a Drug-Induced Bone Loss Model in Rats

by Nada Oršolić, Johann Nemrava, Željko Jeleč, Marina Kukolj, Dyana Odeh, Boris Jakopović, Maja Jazvinšćak Jembrek, Tomica Bagatin, Rajko Fureš and Dinko Bagatin

Int. J. Mol. Sci. 2022, 23(5), 2872; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23052872 - 06 Mar 2022

Cited by 17 | Viewed by 2545

Abstract

Oxidative stress (OS) mediators, together with the inflammatory processes, are considered as threatening factors for bone health. The aim of this study was to investigate effects of flavonoids naringenin and chrysin on OS, inflammation, and bone degradation in retinoic acid (13cRA)-induced secondary osteoporosis (OP) in rats. We analysed changes in body and uterine weight, biochemical bone parameters (bone mineral density (BMD), bone mineral content (BMC), markers of bone turnover), bone geometry parameters, bone histology, OS parameters, biochemical and haematological parameters, and levels of inflammatory cytokines. Osteoporotic rats had reduced bone Ca and P levels, BMD, BMC, and expression of markers of bone turnover, and increased values of serum enzymes alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). Malondialdehyde (MDA) production in liver, kidney, and ovary was increased, while the glutathione (GSH) content and activities of antioxidant enzymes were reduced and accompanied with the enhanced release of inflammatory mediators TNF-α, IL-1β, IL-6, and RANTES chemokine (regulated on activation normal T cell expressed and secreted) in serum. Treatment with chrysin or naringenin improved bone quality, reduced bone resorption, and bone mineral deposition, although with a lower efficacy compared with alendronate. However, flavonoids exhibited more pronounced antioxidative, anti-inflammatory and phytoestrogenic activities, indicating their great potential in attenuating bone loss and prevention of OP. Full article

(This article belongs to the Special Issue The Role of Natural Compounds in Osteoblastic and Osteoclastic Cells)

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16 pages, 8200 KiB

Open AccessArticle

Aesculetin Accelerates Osteoblast Differentiation and Matrix-Vesicle-Mediated Mineralization

by Woojin Na, Min-Kyung Kang, Sin-Hye Park, Dong Yeon Kim, Su Yeon Oh, Moon-Sik Oh, Sohyun Park, II-Jun Kang and Young-Hee Kang

Int. J. Mol. Sci. 2021, 22(22), 12391; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222212391 - 17 Nov 2021

Cited by 8 | Viewed by 3342

Abstract

The imbalance between bone resorption and bone formation in favor of resorption results in bone loss and deterioration of bone architecture. Osteoblast differentiation is a sequential event accompanying biogenesis of matrix vesicles and mineralization of collagen matrix with hydroxyapatite crystals. Considerable efforts have been made in developing naturally-occurring plant compounds, preventing bone pathologies, or enhancing bone regeneration. Coumarin aesculetin inhibits osteoporosis through hampering the ruffled border formation of mature osteoclasts. However, little is known regarding the effects of aesculetin on the impairment of matrix vesicle biogenesis. MC3T3-E1 cells were cultured in differentiation media with 1–10 μM aesculetin for up to 21 days. Aesculetin boosted the bone morphogenetic protein-2 expression, and alkaline phosphatase activation of differentiating MC3T3-E1 cells. The presence of aesculetin strengthened the expression of collagen type 1 and osteoprotegerin and transcription of Runt-related transcription factor 2 in differentiating osteoblasts for 9 days. When ≥1–5 μM aesculetin was added to differentiating cells for 15–18 days, the induction of non-collagenous proteins of bone sialoprotein II, osteopontin, osteocalcin, and osteonectin was markedly enhanced, facilitating the formation of hydroxyapatite crystals and mineralized collagen matrix. The induction of annexin V and PHOSPHO 1 was further augmented in ≥5 μM aesculetin-treated differentiating osteoblasts for 21 days. In addition, the levels of tissue-nonspecific alkaline phosphatase and collagen type 1 were further enhanced within the extracellular space and on matrix vesicles of mature osteoblasts treated with aesculetin, indicating matrix vesicle-mediated bone mineralization. Finally, aesculetin markedly accelerated the production of thrombospondin-1 and tenascin C in mature osteoblasts, leading to their adhesion to preformed collagen matrix. Therefore, aesculetin enhanced osteoblast differentiation, and matrix vesicle biogenesis and mineralization. These findings suggest that aesculetin may be a potential osteo-inductive agent preventing bone pathologies or enhancing bone regeneration. Full article

(This article belongs to the Special Issue The Role of Natural Compounds in Osteoblastic and Osteoclastic Cells)

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10 pages, 23715 KiB

Open AccessArticle

Anti-Osteoporotic Effect of Morroniside on Osteoblast and Osteoclast Differentiation In Vitro and Ovariectomized Mice In Vivo

by Chang Gun Lee, Jeonghyun Kim, Seung Hee Yun, Seokjin Hwang, Hyoju Jeon, Eunkuk Park and Seon-Yong Jeong

Int. J. Mol. Sci. 2021, 22(19), 10642; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910642 - 30 Sep 2021

Cited by 15 | Viewed by 2260

Abstract

Bone remodeling is a continuous process of bone synthesis and destruction that is regulated by osteoblasts and osteoclasts. Here, we investigated the anti-osteoporotic effects of morroniside in mouse preosteoblast MC3T3-E1 cells and mouse primary cultured osteoblasts and osteoclasts in vitro and ovariectomy (OVX)-induced mouse osteoporosis in vivo. Morroniside treatment enhanced alkaline phosphatase activity and positively stained cells via upregulation of osteoblastogenesis-associated genes in MC3T3-E1 cell lines and primary cultured osteoblasts. However, morroniside inhibited tartrate-resistant acid phosphatase activity and TRAP-stained multinucleated positive cells via downregulation of osteoclast-mediated genes in primary cultured monocytes. In the osteoporotic animal model, ovariectomized (OVX) mice were administered morroniside (2 or 10 mg/kg/day) for 12 weeks. Morroniside prevented OVX-induced bone mineral density (BMD) loss and reduced bone structural compartment loss in the micro-CT images. Taken together, morroniside promoted increased osteoblast differentiation and decreased osteoclast differentiation in cells, and consequently inhibited OVX-induced osteoporotic pathogenesis in mice. This study suggests that morroniside may be a potent therapeutic single compound for the prevention of osteoporosis. Full article

(This article belongs to the Special Issue The Role of Natural Compounds in Osteoblastic and Osteoclastic Cells)

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14 pages, 3501 KiB

Open AccessArticle

Effects of 4-Hexylresorcinol on Craniofacial Growth in Rats

by In-Song Lee, Dae-Won Kim, Ji-Hyeon Oh, Suk Keun Lee, Je-Yong Choi, Seong-Gon Kim and Tae-Woo Kim

Int. J. Mol. Sci. 2021, 22(16), 8935; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168935 - 19 Aug 2021

Cited by 7 | Viewed by 1846

Abstract

4-Hexylresorcinol (4HR) has been used as a food additive, however, it has been recently demonstrated as a Class I histone deacetylase inhibitor (HDACi). Unlike other HDACi, 4HR can be taken through foods. Unfortunately, some HDACi have an influence on craniofacial growth, therefore, the purpose of this study was to evaluate the effects of 4HR on craniofacial growth. Saos-2 cells (osteoblast-like cells) were used for the evaluation of HDACi and its associated activities after 4HR administration. For the evaluation of craniofacial growth, 12.8 mg/kg of 4HR was administered weekly to 4 week old rats (male: 10, female: 10) for 12 weeks. Ten rats were used for untreated control (males: 5, females: 5). Body weight was recorded every week. Serum and head samples were collected at 12 weeks after initial administration. Craniofacial growth was evaluated by micro-computerized tomography. Serum was used for ELISA (testosterone and estrogen) and immunoprecipitation high-performance liquid chromatography (IP-HPLC). The administration of 4HR (1–100 μM) showed significant HDACi activity (p < 0.05). Body weight was significantly different in male rats (p < 0.05), and mandibular size was significantly smaller in 4HR-treated male rats with reduced testosterone levels. However, the mandibular size was significantly higher in 4HR treated female rats with increased growth hormone levels. In conclusion, 4HR had HDACi activity in Saos-2 cells. The administration of 4HR on growing rats showed different responses in body weight and mandibular size between sexes. Full article

(This article belongs to the Special Issue The Role of Natural Compounds in Osteoblastic and Osteoclastic Cells)

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Review

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32 pages, 2416 KiB

Open AccessReview

A Review on the Molecular Mechanisms of Action of Natural Products in Preventing Bone Diseases

by Innocent U. Okagu, Timothy P. C. Ezeorba, Rita N. Aguchem, Ikenna C. Ohanenye, Emmanuel C. Aham, Sunday N. Okafor, Carlotta Bollati and Carmen Lammi

Int. J. Mol. Sci. 2022, 23(15), 8468; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23158468 - 30 Jul 2022

Cited by 12 | Viewed by 4283

Abstract

The drugs used for treating bone diseases (BDs), at present, elicit hazardous side effects that include certain types of cancers and strokes, hence the ongoing quest for the discovery of alternatives with little or no side effects. Natural products (NPs), mainly of plant origin, have shown compelling promise in the treatments of BDs, with little or no side effects. However, the paucity in knowledge of the mechanisms behind their activities on bone remodeling has remained a hindrance to NPs’ adoption. This review discusses the pathological development of some BDs, the NP-targeted components, and the actions exerted on bone remodeling signaling pathways (e.g., Receptor Activator of Nuclear Factor κ B-ligand (RANKL)/monocyte/macrophage colony-stimulating factor (M-CSF)/osteoprotegerin (OPG), mitogen-activated protein kinase (MAPK)s/c-Jun N-terminal kinase (JNK)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), Kelch-like ECH-associated protein 1 (Keap-1)/nuclear factor erythroid 2–related factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1), Bone Morphogenetic Protein 2 (BMP2)-Wnt/β-catenin, PhosphatidylInositol 3-Kinase (PI3K)/protein kinase B (Akt)/Glycogen Synthase Kinase 3 Beta (GSK3β), and other signaling pathways). Although majority of the studies on the osteoprotective properties of NPs against BDs were conducted ex vivo and mostly on animals, the use of NPs for treating human BDs and the prospects for future development remain promising. Full article

(This article belongs to the Special Issue The Role of Natural Compounds in Osteoblastic and Osteoclastic Cells)

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