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Bone Cell Biology and Transcriptional Regulation

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Oncology".

Deadline for manuscript submissions: closed (31 December 2016) | Viewed by 31697

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Special Issue Editor

Assoc. Prof. Hirohiko Okamura

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Guest Editor

Department of Histology and Oral Histology, Institute of Biomedical Sciences, University of Tokushima Graduate School, Tokushima, Japan
Interests: differentiation and transcriptional regulator Osterix of the osteoblasts; dephosphorylation enzyme inhibitor and apoptosis by the transcriptional regulators

Special Issue Information

Dear Colleagues,

Bone tissue is constantly changing to achieve both calcium homeostasis and structural integrity under the physiological conditions. However, the imbalance between bone formation and resorption results in various diseases including osteoporosis and periodontal diseases. Homeostasis in bone tissue is the result of a delicate balance between bone formation by osteoblasts and bone resorption by osteoclasts. Osteoblasts originate from a common progenitor cell with adipocytes, bone marrow mesenchymal stem cells, whereas osteoclasts are derived from hematopoietic stem cell precursors along the myeloid differentiation lineage. The differentiation and function of these cells are all governed by several transcription factors through epigenetic modification, resulting in the expression of bonespecific genes. Protein phosphorylation by kinases and dephosphorylation by phosphatases has been recognized as an essential mechanism in the regulation of protein function and eventually cellular metabolism in various tissues. Recently, many studies have discovered the potential roles of protein kinases and phosphatases in the differentiation and function of bone cells. The aim of the Special Issue article is to provide the reader with the latest information concerning osteoblast and osteoclast biology, with emphasis on the control by protein phosphorylation. The articles and reviews about the role of protein kinases and phosphatases in bone tumors, such as osteosarcoma and myeloma, are also discussed in this Special Issue.

Assoc. Prof. Hirohiko Okamura
Guest Editor

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Keywords

osteoblast
osteoclast
protein kinase
protein phosphatase
bone metabolism
bone
tumor
epigenetic regulation
transcription factor

Published Papers (5 papers)

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Research

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1422 KiB

Open AccessArticle

In Vitro and In Vivo Effects of Gracilaria verrucosa Extracts on Osteoclast Differentiation

by Kwang-Jin Kim, Yong-Jin Lee, Yun-Ho Hwang, Kyung-Yun Kang, Sung-Tae Yee and Young-Jin Son

J. Clin. Med. 2017, 6(3), 32; https://doi.org/10.3390/jcm6030032 - 14 Mar 2017

Cited by 64 | Viewed by 4596

Abstract

Bone remodeling, a physiological process characterized by bone formation by osteoblasts and bone resorption by osteoclasts, is important for the maintenance of healthy bone in adult humans. Osteoclasts play a critical role in bone erosion and osteoporosis and are bone-specific multinucleated cells generated through differentiation of monocyte/macrophage lineage precursors. Receptor activator of NF-κB ligand (RANKL) has been reported to induce osteoclast differentiation. In this study, we explored whether Gracilaria verrucosa extracts (GE) could affect RANKL-mediated osteoclast differentiation. GE significantly inhibited RANKL-activated osteoclast differentiation by inhibiting protein expression of c-fos and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), vital factors in RANKL-mediated osteoclastogenesis. In addition, GE attenuated ovariectomy-induced bone loss in mice. In summary, GE can prevent osteoclastogenesis and hormone-related bone loss via blockage of c-fos-NFATc1 signaling. Our results suggest that GE may have therapeutic potential in the treatment of postmenopausal osteoporosis. Full article

(This article belongs to the Special Issue Bone Cell Biology and Transcriptional Regulation)

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1586 KiB

Open AccessArticle

Combined Effects of Androgen and Growth Hormone on Osteoblast Marker Expression in Mouse C2C12 and MC3T3-E1 Cells Induced by Bone Morphogenetic Protein

by Kosuke Kimura, Tomohiro Terasaka, Nahoko Iwata, Takayuki Katsuyama, Motoshi Komatsubara, Ryota Nagao, Kenichi Inagaki and Fumio Otsuka

J. Clin. Med. 2017, 6(1), 6; https://doi.org/10.3390/jcm6010006 - 05 Jan 2017

Cited by 5 | Viewed by 7349

Abstract

Osteoblasts undergo differentiation in response to various factors, including growth factors and steroids. Bone mass is diminished in androgen- and/or growth hormone (GH)-deficient patients. However the functional relationship between androgen and GH, and their combined effects on bone metabolism, remains unclear. Here we investigated the mutual effects of androgen and GH on osteoblastic marker expression using mouse myoblastic C2C12 and osteoblast-like MC3T3-E1 cells. Combined treatment with dihydrotestosterone (DHT) and GH enhanced BMP-2-induced expression of Runx2, ALP, and osteocalcin mRNA, compared with the individual treatments in C2C12 cells. Co-treatment with DHT and GH activated Smad1/5/8 phosphorylation, Id-1 transcription, and ALP activity induced by BMP-2 in C2C12 cells but not in MC3T3-E1 cells. The insulin-like growth factor (IGF-I) mRNA level was amplified by GH and BMP-2 treatment and was restored by co-treatment with DHT in C2C12 cells. The mRNA level of the IGF-I receptor was not significantly altered by GH or DHT, while it was increased by IGF-I. In addition, IGF-I treatment increased collagen-1 mRNA expression, whereas blockage of endogenous IGF-I activity using an anti-IGF-I antibody failed to suppress the effect of GH and DHT on BMP-2-induced Runx2 expression in C2C12 cells, suggesting that endogenous IGF-I was not substantially involved in the underlying GH actions. On the other hand, androgen receptor and GH receptor mRNA expression was suppressed by BMP-2 in both cell lines, implying the existence of a feedback action. Collectively the results showed that the combined effects of androgen and GH facilitated BMP-2-induced osteoblast differentiation at an early stage by upregulating BMP receptor signaling. Full article

(This article belongs to the Special Issue Bone Cell Biology and Transcriptional Regulation)

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2331 KiB

Open AccessArticle

Hyaluronic Acid Gel-Based Scaffolds as Potential Carrier for Growth Factors: An In Vitro Bioassay on Its Osteogenic Potential

by Masako Fujioka-Kobayashi, Benoit Schaller, Eizaburo Kobayashi, Maria Hernandez, Yufeng Zhang and Richard J. Miron

J. Clin. Med. 2016, 5(12), 112; https://doi.org/10.3390/jcm5120112 - 30 Nov 2016

Cited by 19 | Viewed by 6245

Abstract

Hyaluronic acid (HA) has been utilized for a variety of regenerative medical procedures due to its widespread presence in connective tissue and perceived biocompatibility. The aim of the present study was to investigate HA in combination with recombinant human bone morphogenetic protein 9 (rhBMP9), one of the most osteogenic growth factors of the BMP family. HA was first combined with rhBMP9 and assessed for the adsorption and release of rhBMP9 over 10 days by ELISA. Thereafter, ST2 pre-osteoblasts were investigated by comparing (1) control tissue culture plastic, (2) HA alone, and (3) HA with rhBMP9 (100 ng/mL). Cellular proliferation was investigated by a MTS assay at one, three and five days and osteoblast differentiation was investigated by alkaline phosphatase (ALP) activity at seven days, alizarin red staining at 14 days and real-time PCR for osteoblast differentiation markers. The results demonstrated that rhBMP9 adsorbed within HA scaffolds and was released over a 10-day period in a controlled manner. While HA and rhBMP9 had little effect on cell proliferation, a marked and pronounced effect was observed for cell differentiation. rhBMP9 significantly induced ALP activity, mRNA levels of collagen1α2, and ALP and osteocalcin (OCN) at three or 14 days. HA also demonstrated some ability to induce osteoblast differentiation by increasing mRNA levels of OCN and increasing alizarin red staining at 14 days. In conclusion, the results from the present study demonstrate that (1) HA may serve as a potential carrier for various growth factors, and (2) rhBMP9 is a potent and promising inducer of osteoblast differentiation. Future animal studies are now necessary to investigate this combination approach in vivo. Full article

(This article belongs to the Special Issue Bone Cell Biology and Transcriptional Regulation)

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Review

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374 KiB

Open AccessReview

The Roles of Histone Demethylase Jmjd3 in Osteoblast Differentiation and Apoptosis

by Di Yang, Bo Yu, Haiyan Sun and Lihong Qiu

J. Clin. Med. 2017, 6(3), 24; https://doi.org/10.3390/jcm6030024 - 23 Feb 2017

Cited by 15 | Viewed by 5435

Abstract

Posttranslational modifications including histone methylation regulate gene transcription through directly affecting the structure of chromatin. Trimethylation of histone 3 lysine 27 (H3K27me3) is observed at the promoters of a wide variety of important genes, especially for mammalian development, and contributes to gene silencing. Demethylase Jumonji domain-containing 3 (Jmjd3) catalyzes the transition of H3K27me3 to H3K27me1, therefore from a repressive to an active status of gene expression. Jmjd3 plays important roles in cell differentiation, inflammation, and tumorigenesis by targeting distinct transcription factors. In this review, we summarize the pivotal roles of Jmjd3 in maintaining skeletal homeostasis through regulating osteoblast differentiation, maturation, and apoptosis. Full article

(This article belongs to the Special Issue Bone Cell Biology and Transcriptional Regulation)

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848 KiB

Open AccessFeature PaperReview

Role of Protein Phosphatase 2A in Osteoblast Differentiation and Function

by Hirohiko Okamura, Kaya Yoshida, Hiroyuki Morimoto, Jumpei Teramachi, Kazuhiko Ochiai, Tatsuji Haneji and Akihito Yamamoto

J. Clin. Med. 2017, 6(3), 23; https://doi.org/10.3390/jcm6030023 - 23 Feb 2017

Cited by 16 | Viewed by 7570

Abstract

The reversible phosphorylation of proteins plays hugely important roles in a variety of cellular processes, such as differentiation, proliferation, and apoptosis. These processes are strictly controlled by protein kinases (phosphorylation) and phosphatases (de-phosphorylation). Here we provide a brief history of the study of protein phosphorylation, including a summary of different types of protein kinases and phosphatases. One of the most physiologically important serine/threonine phosphatases is PP2A. This review provides a description of the phenotypes of various PP2A transgenic mice and further focuses on the known functions of PP2A in bone formation, including its role in osteoblast differentiation and function. A reduction in PP2A promotes bone formation and osteoblast differentiation through the regulation of bone-related transcription factors such as Osterix. Interestingly, downregulation of PP2A also stimulates adipocyte differentiation from undifferentiated mesenchymal cells under the appropriate adipogenic differentiation conditions. In osteoblasts, PP2A is also involved in the ability to control osteoclastogenesis as well as in the proliferation and metastasis of osteosarcoma cells. Thus, PP2A is considered to be a comprehensive factor in controlling the differentiation and function of cells derived from mesenchymal cells such as osteoblasts and adipocytes. Full article

(This article belongs to the Special Issue Bone Cell Biology and Transcriptional Regulation)

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