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Munkhsoyol Erkhembaatar,Hyuncheol Oh,Min Seuk Kim KOREAN ACADAMY OF ORAL BIOLOGY 2014 International Journal of Oral Biology Vol.39 No.1
Streptococcus mutans (S. mutans) is a facultative anaerobic bacterium mainly found in the oral cavity and is known to contribute to tooth decay and gingivitis. Recent studies on intestinal microbiota have revealed that microorganisms forming a biofilm play important roles in maintaining tissue homeostasis through their own metabolism. However, the physiological roles of oral microorganisms such as S. mutans are still unclear. In our current study, we identified that constituents released from S. mutans (CR) reduce arecolinemediated cytotoxicity without producing toxic effects themselves. Arecoline, as a major alkaloid of areca nut, is known to mediate cytotoxicity on oral epithelial cells and induces a sustained intracellular Ca2+ ([Ca2+]i) increase that is cytotoxic. The exposure of human gingival fibroblast (HGF) cells to CR not only inhibited the sustained [Ca2+]i increase but also the initial [Ca2+]i elevation. In contrast, CR had no effects on the gene regulation mediated by arecoline. These results demonstrate that S. mutans has physiological role in reducing cytotoxicity in HGF cells and may be considered a novel pharmaceutical candidate.
Erkhembaatar, Munkhsoyol,Gu, Dong Ryun,Lee, Seoung Hoon,Yang, Yu-Mi,Park, Soonhong,Muallem, Shmuel,Shin, Dong Min,Kim, Min Seuk Wiley-Blackwell Publishing, Inc. 2017 Journal of Bone and Mineral Research Vol. No.
<P>Lysosomal Ca2+ emerges as a critical component of receptor-evoked Ca2+ signaling and plays a crucial role in many lysosomal and physiological functions. Lysosomal Ca2+ release is mediated by the transient receptor potential (TRP) family member TRPML1, mutations that cause the lysosomal storage disease mucolipidosis type 4. Lysosomes play a key role in osteoclast function. However, nothing is known about the role of lysosomal Ca2+ signaling in osteoclastogenesis and bone metabolism. In this study, we addressed this knowledge gap by studying the role of lysosomal Ca2+ signaling in osteoclastogenesis, osteoclast and osteoblast functions, and bone homeostasis in vivo. We manipulated lysosomal Ca2+ signaling by acute knockdown of TRPML1, deletion of TRPML1 in mice, pharmacological inhibition of lysosomal Ca2+ influx, and depletion of lysosomal Ca2+ storage using the TRPML agonist ML-SA1. We found that knockdown and deletion of TRPML1, although it did not have an apparent effect on osteoblast differentiation and bone formation, markedly attenuated osteoclast function, RANKL-induced cytosolic Ca2+ oscillations, inhibited activation of NFATc1 and osteoclastogenesis-controlling genes, suppressed the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs), and markedly reduced the differentiation of bone marrow-derived macrophages into osteoclasts. Moreover, deletion of TRPML1 resulted in enlarged lysosomes, inhibition of lysosomal secretion, and attenuated the resorptive activity of mature osteoclasts. Notably, depletion of lysosomal Ca2+ with ML-SA1 similarly abrogated RANKL-induced Ca2+ oscillations and MNC formation. Deletion of TRPML1 in mice reduced the TRAP-positive bone surfaces and impaired bone remodeling, resulting in prominent osteopetrosis. These findings demonstrate the essential role of lysosomal Ca2+ signaling in osteoclast differentiation and mature osteoclast function, which play key roles in bone homeostasis. (C) 2016 American Society for Bone and Mineral Research.</P>
Peucedanum japonicum Thunb. ethanol extract suppresses RANKL-mediated osteoclastogenesis
Kim, Jeong-Mi,Erkhembaatar, Munkhsoyol,Lee, Guem-San,Lee, Jin-Hyun,Noh, Eun-Mi,Lee, Minok,Song, Hyun-Kyung,Lee, Choong Hun,Kwon, Kang-Beom,Kim, Min Seuk,Lee, Young-Rae Spandidos Publications 2017 Experimental and therapeutic medicine Vol.14 No.1
Oh, Seunghan,Choi, Eun-Joo,Erkhembaatar, Munkhsoyol,Kim, Min Seuk Hindawi Limited 2015 Journal of nanomaterials Vol.2015 No.-
<P>Titanium (Ti) possesses excellent properties for use in dental implants but has low osteogenic surface properties that result in limiting rapid osseointegration. The physiological interaction between the surface of the implant material and bone cells, especially osteoclasts, is a crucial factor in determining successful osseointegration. However, the details of such an interaction remain elusive. Here, we demonstrated that nanotopography on the Ti surface is a crucial factor for modulating intracellular signal transduction in bone marrow-derived macrophages (BMMs). To define this, intracellular Ca<SUP>2+</SUP>and ROS were simultaneously measured in BMMs that were seeded on polished Ti and TiO2nanotubes. We found that UV photocatalysis of TiO2immediately elicits intracellular calcium concentration ([Ca<SUP>2+</SUP>]i) increase and intracellular reactive oxygen species concentration ([ROS]i) reduction in cells on TiO2nanotubes. UV photocatalysis-mediated [Ca<SUP>2+</SUP>]iincrease is dependent on extracellular and intracellular ROS generation. Furthermore, extracellular Ca<SUP>2+</SUP>influx through voltage-gated calcium channels (VGCCs) is critical for the UV photocatalysis-mediated [Ca<SUP>2+</SUP>]iincrease, while phospholipase C (PLC) activation is not required. Considering the physiological roles of Ca<SUP>2+</SUP>signaling in BMMs and osteoclastogenesis, nanotopography on the Ti surface should be considered an important factor that can influence successful dental implantation.</P>
Gu, Dong Ryun,Hwang, Jin-Ki,Erkhembaatar, Munkhsoyol,Kwon, Kang-Beom,Kim, Min Seuk,Lee, Young-Rae,Lee, Seoung Hoon Hindawi Publishing Corporation 2013 Evidence-based Complementary and Alternative Medic Vol.2013 No.-
<P><I>Chrysanthemum zawadskii Herbich</I> var. <I>latilobum Kitamura</I>, known as “Gujulcho” in Korea, has been used in traditional medicine to treat various inflammatory diseases, including rheumatoid arthritis. However, these effects have not been tested on osteoclasts, the bone resorbing cells that regulate bone metabolism. Here, we investigated the effects of <I>C. zawadskii</I> Herbich var. <I>latilobum</I> Kitamura ethanol extract (CZE) on osteoclast differentiation induced by treatment with the receptor activator of NF-<I><I>κ</I></I>B ligand (RANKL). CZE inhibited osteoclast differentiation and formation in a dose-dependent manner. The inhibitory effect of CZE on osteoclastogenesis was due to the suppression of ERK activation and the ablation of RANKL-stimulated Ca<SUP>2+</SUP>-oscillation via the inactivation of PLC<I><I>γ</I></I>2, followed by the inhibition of CREB activation. These inhibitory effects of CZE resulted in a significant repression of c-Fos expression and a subsequent reduction of NFATc1, a key transcription factor for osteoclast differentiation, fusion, and activation <I>in vitro</I> and <I>in vivo</I>. These results indicate that CZE negatively regulates osteoclast differentiation and may be a therapeutic candidate for the treatment of various bone diseases, such as postmenopausal osteoporosis, rheumatoid arthritis, and periodontitis.</P>
Kim, Ju-Young,Park, Sun-Hyang,Baek, Jong Min,Erkhembaatar, Munkhsoyol,Kim, Min Seuk,Yoon, Kwon-Ha,Oh, Jaemin,Lee, Myeung Su American Chemical Society and American Society of 2015 Journal of natural products Vol.78 No.9
<P>Harpagoside (HAR) is a natural compound isolated from <I>Harpagophytum procumbens</I> (devil’s claw) that is reported to have anti-inflammatory effects; however, these effects have not been investigated in the context of bone development. The current study describes for the first time that HAR inhibits receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis <I>in vitro</I> and suppresses inflammation-induced bone loss in a mouse model. HAR also inhibited the formation of osteoclasts from mouse bone marrow macrophages (BMMs) in a dose-dependent manner as well as the activity of mature osteoclasts, including filamentous actin (F-actin) ring formation and bone matrix breakdown. This involved a HAR-induced decrease in extracellular signal-regulated kinase (ERK) and c-jun N-terminal kinase (JNK) phosphorylation, leading to the inhibition of Syk-Btk-PLCγ2-Ca<SUP>2+</SUP> in RANKL-dependent early signaling, as well as the activation of c-Fos and nuclear factor of activated T cells cytoplasmic 1 (NFATc1), which resulted in the down-regulation of various target genes. Consistent with these <I>in vitro</I> results, HAR blocked lipopolysaccharide (LPS)-induced bone loss in an inflammatory osteoporosis model. However, HAR did not prevent ovariectomy-mediated bone erosion in a postmenopausal osteoporosis model. These results suggest that HAR is a valuable agent against inflammation-related bone disorders but not osteoporosis induced by hormonal abnormalities.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jnprdf/2015/jnprdf.2015.78.issue-9/acs.jnatprod.5b00233/production/images/medium/np-2015-002336_0007.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/np5b00233'>ACS Electronic Supporting Info</A></P>
Jung-Hoon Kim,Min Seuk Kim,Hong-Geun Oh,Hak-Yong Lee,Jeong-Woo Park,Bong-Gun Lee,Sang-Hoon Park,Dae-In Moon,Eun-Hye Shin,Eun-Kyeong Oh,Munkhsoyol Erkhembaatar,Okjin Kim,Yong-Rae Lee,Han-Jung Chae 한국실험동물학회 2013 Laboratory Animal Research Vol.29 No.2
It has been generally accepted that calcium intake prevents bone loss, and frequent fracture resulted from osteoporosis. However, it is still elusive as to how effective sole calcium intake is in preventing or attenuating the severity of osteoporosis. Here, we demonstrate the effects of eggshell-casein phosphopeptide (ES-CPP), and compared these effects those of calcium supplement, for restoring ovariectomy-mediated bone loss. CPP, synthesized from the hydrolysis of casein (0.5%) using trypsin, was added to the grinded ES and was then administered to the ovariectomized (OVX) rat at 100 mg/kg for 4 weeks. Urine and feces from each group were collected each day, and were used to calculate the apparent calcium absorption rate in a day. After 4 weeks incubation, blood and femoral bones were isolated for the analysis of parameters representing osteoporosis. The apparent calcium absorption rate was significantly increased in the ES-CPP treated groups, in comparison to both the OVX and the commercial calcium supplement (CCS) treated group. Notably, treatment with ES-CPP markedly enhanced the calcium content in femoral bone and the relative weight of femoral bone to body weight, though calcium content in serum was barely changed by treatment with ES-CPP. Parameters of osteoporosis, such as osteocalcin in serum and bone mineral density, were rescued by treatment with ES-CPP, compared to treatment with commercial calcium supplement. This finding strongly suggests the possible use of ES-CPP in preventing or attenuating the severity of postmenopausal osteoporosis.