• Journal of Food Hygiene and Safety
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• v.37 no.5
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• pp.364-371
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• 2022

The bones of the human body support the structures of the body and provide protection for a person's internal organs. Bone metabolic diseases are on the rise due to a significant increase in life expectancy over a short period of time. Therefore, we investigated the osteoblast differentiation promoting and osteoclastogenesis inhibitory activities of fermented Benincasa hispida cong. (HR1901-BS, HR1901-BSaf). We evaluated the alkaline phosphatase (ALP) activity of MC3T3-E1 mouse calvarial-derived osteoblasts. We also evaluated expression of ALP, osteocalcin (OCN), and runt-related transcription factor 2 (Runx2), which regulate osteoblast differentiation. To assess effects on osteoclast formation, tartrate-resistant acid phosphatase (TRAP) activity in RAW264.7 cells was analyzed. ALP activity increased by 121-136% and 140-156%, respectively in the presence of HR1901-BS and HR1901-BSaf. Expression of osteoblast differentiation factor also increased significantly. We also confirmed that HR1901-BS and HR1901-BSaf decreased TRAP activity in osteoclasts by 35-47% and 23-39%, respectively. Our results showed that fermented Benincasa hispida cong. (HR1901-BS, HR1901-BSaf) increase bone mineralization and osteoblast differentiation activity in MC3T3-E1 cells, and inhibit bone resorption activity in RAW264.7 cells. In conclusion, fermented Benincasa hispida cong. (HR1901-BS, HR1901-BSaf) can be used as an effective natural resource for preventing and treating bone-related diseases.

• Journal of Nutrition and Health
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• v.51 no.5
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• pp.379-385
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• 2018

Purpose: Zinc (Zn) is an essential trace element for bone mineralization and osteoblast function. We examined the effects of Zn deficiency on osteoblast differentiation and mineralization in MC3T3-E1 cells. Methods: Osteoblastic MC3T3-E1 cells were cultured at concentration of 1 to $15{\mu}M$ $ZnCl_2$ (Zn- or Zn+) for 5, 15 and 25 days up to the calcification period. Extracellular matrix mineralization was detected by staining Ca and P deposits using Alizarin Red and von Kossa stain respectively, and alkaline phosphatase (ALP) activity was detected by ALP staining and colorimetric method. Results: Extracellular matrix mineralization was decreased in Zn deficiency over 5, 15, and 25 days. Similarly, staining of ALP activity as the sign of an osteoblast differentiation, was also decreased by Zn deficiency over the same period. Interestingly, the gene expression of bone-related markers (ALP, PTHR; parathyroid hormone receptor, OPN; osteopontin, OC; osteocalcin and COLI; collagen type I), and bone-specific transcription factor Runx2 were downregulated by Zn deficiency for 5 or 15 days, however, this was restored at 25 days. Conclusion: Our data suggests that Zn deficiency inhibits osteoblast differentiation by retarding bone marker gene expression and also inhibits bone mineralization by decreasing Ca/P deposition as well as ALP activity.

• BMB Reports
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• v.51 no.3
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• pp.126-133
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• 2018

Hippo signaling plays critical roles in regulation of tissue homeostasis, organ size, and tumorigenesis by inhibiting YES-associated protein (YAP) and PDZ-binding protein TAZ through MST1/2 and LATS1/2 pathway. It is also engaged in cross-talk with various other signaling pathways, including WNT, BMPs, Notch, GPCRs, and Hedgehog to further modulate activities of YAP/TAZ. Because YAP and TAZ are transcriptional coactivators that lack DNA-binding activity, both proteins must interact with DNA-binding transcription factors to regulate target gene's expression. To activate target genes involved in cell proliferation, TEAD family members are major DNA-binding partners of YAP/TAZ. Accordingly, YAP/TAZ were originally classified as oncogenes. However, YAP might also play tumor-suppressing role. For example, YAP can bind to DNA-binding tumor suppressors including RUNXs and p73. Thus, YAP might act either as an oncogene or tumor suppressor depending on its binding partners. Here, we summarize roles of YAP depending on its DNA-binding partners and discuss context-dependent functions of YAP/TAZ.

• Proceedings of the Korean Society for Agricultural Machinery Conference
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• 2017.04a
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• pp.109-109
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• 2017

Cirsium setidens nakai belonging to cirsium has been reported to have various physiological activities including anticancer activity because it contains polyphenols, dietary fiber, minerals and vitamins. Despite these positive positive efficacies, however, no studies have studied cirsium setidens nakai products as biomaterials such as cellular metabolism and bone formation. Thus, the aim of this study was evaluate of osteogenesis differentiation a natural material extracted from cirsium setidens nakai. The natural materials in this studys in this studywere created by 40% ethanol extraction process and then dried. FabricatedFabricatedpowders were added to a medium at various concentrations (0.01, 0.05, 0.1, 0.2, and $0.25{\mu}g/mL$), and pure medium was used as a control. The natural material caused positive increases in cell metabolic activity and mineralized bone formation without cytotoxicity. In addition, we observed higher expression of genes such as ALP, BSP, Runx2 and COL1 in cirsium setidens nakai treatment cells. As a result, this study produced and investigated cirsium setidens nakai extracts and the natural materials showed potential biomaterials. In this research indicated that the cirsium setidens nakai extracts might have promising applications in areas of agricultural, biological and food engineering as a biomaterial.

• Molecules and Cells
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• v.25 no.1
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• pp.1-6
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• 2008

Osteoarthritis (OA), one of the most common skeletal disorders characterized by cartilage degradation and osteophyte formation in joints, is induced by accumulated mechanical stress; however, little is known about the underlying molecular mechanism. Several experimental OA models in mice by producing instability in the knee joints have been developed to apply approaches from mouse genetics. Although proteinases like matrix metalloproteinases and aggrecanases have now been proven to be the principal initiators of OA progression, clinical trials of proteinase inhibitors have not been successful for the treatment, turning the interest of researchers to the upstream signals of proteinase induction. These signals include undegraded and fragmented matrix proteins like type II collagen or fibronection that affects chondrocytes through distinct receptors. Another signal is proinflammatory factors that are produced by chondrocytes and synovial cells; however, recent studies that used mouse OA models in knockout mice did not support that these factors have a role in the central contribution to OA development. Our mouse genetic approaches found that the induction of a transcriptional activator Runx2 in chondrocytes under mechanical stress contributes to the pathogenesis of OA through chondrocyte hypertrophy. In addition, chondrocyte apoptosis has recently been identified as being involved in OA progression. We hereby propose that these endochondral ossification signals may be important for the OA progression, suggesting that the related molecules can clinically be therapeutic targets of this disease.

• The korean journal of orthodontics
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• v.43 no.5
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• pp.248-260
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• 2013

Cleidocranial dysplasia (CCD), an autosomal dominant disorder with a prevalence of 1 in 1,000,000 individuals, is mainly caused by mutations in Runx2, a gene required for osteoblastic differentiation. It is generally characterized by hypoplastic clavicles, narrow thorax, and delayed or absent fontanel closure. Importantly, its orofacial manifestations, including midfacial hypoplasia, retained primary teeth, and impacted permanent and supernumerary teeth, severely impede the well-being of affected individuals. Successful treatment of the orofacial problems requires the combined efforts of dental specialists. However, only a few successfully treated cases have been reported because of the rarity of CCD and complexity of the treatment. This article presents the University of California, San Francisco (UCSF) treatment protocol for the dentofacial manifestations of CCD based on two treated and 17 diagnosed cases. The records of two patients with CCD who had been treated at the UCSF School of Dentistry and the treatment options reported in the literature were reviewed. The UCSF treatment protocol produced a successful case and a partially successful one (inadequate oral hygiene in the retention stage resulted in decay and loss of teeth). It provides general guidelines for successfully treating the orofacial manifestations of CCD.

• BMB Reports
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• v.47 no.2
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• pp.110-114
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• 2014

Fibrin is a natural provisional matrix found in wound healing, while type I collagen is a major organic component of bone matrix. Despite the frequent use of fibrin and type I collagen in bone regenerative approaches, their comparative efficacies have not yet been evaluated. In the present study, we compared the effects of fibrin and collagen on the proliferation and differentiation of osteoblasts and protein adsorption. Compared to collagen, fibrin adsorbed approximately 6.7 times more serum fibronectin. Moreover, fibrin allowed the proliferation of larger MC3T3-E1 pre-osteoblasts, especially at a low cell density. Fibrin promoted osteoblast differentiation at higher levels than collagen, as confirmed by Runx2 expression and transcriptional activity, alkaline phosphatase activity, and calcium deposition. The results of the present study suggest that fibrin is superior to collagen in the support of bone regeneration.

• Korean Journal of Pharmacognosy
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• v.46 no.4
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• pp.309-314
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• 2015

Periodontitis is a chronic inflammatory disease that is known to have the characteristics of destructed periodontal tissue. Anti-oxidant and anti-inflammatory effects of mulberry leaves in periodontal tissue is not well known until now. We investigated the effects of n-butanol extract of mulberry leaves on the lipopolysaccharide (LPS)-induced proinflammatory cytokines, such as $IL-1{\beta}$, IL-6, IL-8 and modulates osteogenic differentiation in periodontal ligament cells. The expression levels of Runx2, ALP and mRNA were increased by n-butanol extract of mulberry leaves at the concentration of $100{\mu}g/ml$ in periodontal ligament cells. n-Butanol extract of mulberry leaves extract reduced the range of pathophysiological processes, such as inflammation and increase in the level of osteogenic-related genes. These findings suggest that n-butanol extract of mulberry leaves has therapeutic effects on periodontitis and periodontal tissue regeneartion.

• BMB Reports
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• v.52 no.7
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• pp.469-474
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• 2019

Kruppel-like factor 2 (KLF2) has been implicated in the regulation of cell proliferation, differentiation, and survival in a variety of cells. Recently, it has been reported that KLF2 regulates the p65-mediated transactivation of $NF-{\kappa}B$. Although the $NF-{\kappa}B$ pathway plays an important role in the differentiation of osteoclasts and osteoblasts, the role of KLF2 in these bone cells has not yet been fully elucidated. In this study, we demonstrated that KLF2 regulates osteoclast and osteoblast differentiation. The overexpression of KLF2 in osteoclast precursor cells inhibited osteoclast differentiation by downregulating c-Fos, NFATc1, and TRAP expression, while KLF2 overexpression in osteoblasts enhanced osteoblast differentiation and function by upregulating Runx2, ALP, and BSP expression. Conversely, the downregulation of KLF2 with KLF2-specific siRNA increased osteoclast differentiation and inhibited osteoblast differentiation. Moreover, the overexpression of interferon regulatory protein 2-binding protein 2 (IRF2BP2), a regulator of KLF2, suppressed osteoclast differentiation and enhanced osteoblast differentiation and function. These effects were reversed by downregulating KLF2. Collectively, our data provide new insights and evidence to suggest that the IRF2BP2/KLF2 axis mediates osteoclast and osteoblast differentiation, thereby affecting bone homeostasis.

• Molecules and Cells
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• v.24 no.2
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• pp.283-287
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• 2007

$TGF-{\beta}1$ induces Ig germ-line ${\alpha}$ ($GL{\alpha}$) transcription and subsequent class switching recombination (CSR) to IgA. In the present study, we investigated the roles of two E3-ubiquitin ligases, Smurfs (HECT type) and Arkadia (RING finger type) on $TGF{\beta}1$-induced IgA CSR. We found that over-expression of Smurf1 and Smurf2 decreased $TGF{\beta}1$-induced $GL{\alpha}$ promoter activity and strengthened the inhibitory effect of Smad7 on the promoter activity. Further, over-expression of Smurf1 and Smurf2 decreased both Smad3/4-mediated and Runx3-mediated $GL{\alpha}$ promoter activities, suggesting that the Smurfs can down-regulate the major $TGF-{\beta}1$ signaling pathway and decrease $GL{\alpha}$ gene expression. In parallel, the over-expressed Smurf1 decreased the expression of endogenous IgA CSR-predictive transcripts ($GLT_{\alpha}$, $PST_{\alpha}$, and $CT_{\alpha}$) and also $TGF{\beta}1$-induced IgA secretion. Conversely over-expression of Arkadia abolished the inhibitory effect of Smad7 on $TGF{\beta}1$-induced $GLT_{\alpha}$ expression and IgA secretion. Similar results were obtained in the presence of over-expressed Smad7 and Smurf1. These results indicate that Arkadia can amplify $TGF{\beta}1$-induced IgA CSR by degrading Smad7, which interacts with Smurf1. We conclude that Smurf and Arkadia have opposite roles in the regulation of $TGF{\beta}1$-induced IgA isotype expression.