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The Role of Natural Compounds in Osteoblastic and Osteoclastic Cells

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 20960

Special Issue Editors


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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
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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

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Keywords

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

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Published Papers (6 papers)

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Research

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12 pages, 5633 KiB  
Article
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://doi.org/10.3390/ijms232214128 - 16 Nov 2022
Cited by 7 | Viewed by 2074
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 [...] Read more.
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  
Article
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://doi.org/10.3390/ijms23052872 - 6 Mar 2022
Cited by 28 | Viewed by 3322
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 [...] Read more.
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  
Article
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://doi.org/10.3390/ijms222212391 - 17 Nov 2021
Cited by 11 | Viewed by 4049
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 [...] Read more.
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  
Article
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://doi.org/10.3390/ijms221910642 - 30 Sep 2021
Cited by 20 | Viewed by 2769
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 [...] Read more.
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  
Article
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://doi.org/10.3390/ijms22168935 - 19 Aug 2021
Cited by 9 | Viewed by 2263
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 [...] Read more.
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  
Review
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://doi.org/10.3390/ijms23158468 - 30 Jul 2022
Cited by 19 | Viewed by 5287
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 [...] Read more.
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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