• Journal of Ginseng Research
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• v.43 no.4
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• pp.618-624
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• 2019

Background: Ginsenoside Re (Re) is one of the major components of Panax ginseng Meyer. Ginsenoside $Rk_3$ ($Rk_3$) is a secondary metabolite of Re. The aim of this study was to investigate and compare the effects and underlying mechanisms of Re and $Rk_3$ on cyclophosphamide-induced myelosuppression. Methods: The mice myelosuppression model was established by intraperitoneal (i.p.) injection of cyclophosphamide. Peripheral blood cells, bone marrow nucleated cells, and colony yield of hematopoietic progenitor cells in vitro were counted. The levels of erythropoietin, thrombopoietin, and granulocyte macrophage colony-stimulating factor in plasma were measured by enzyme-linked immunosorbent assay. Bone marrow cell cycle was performed by flow cytometry. The expression of apoptotic protein bcl-2, bax, and caspase-3 was detected by Western blotting. Results: Both Re and $Rk_3$ could improve peripheral blood cells, bone marrow nucleated cell counts, thymus index, and spleen index. Furthermore, they could enhance the yield of colonies cultured in vitro and make the levels of granulocyte macrophage colony-stimulating factor, erythropoietin, and thrombopoietin normal, reduce the ratio of $G_0/G_1$ phase cells, and increase the proliferation index. Finally, Re and $Rk_3$ could upregulate the expression of bcl-2, whereas they could downregulate the expression of bax and caspase-3. Conclusion: Re and $Rk_3$ could improve the hematopoietic function of myelosuppressed mice. The effect of $Rk_3$ was superior to that of Re at any dose. Regulating the levels of cytokines, promoting cells enter the normal cell cycle, regulating the balance of bcl-2/bax, and inhibiting the expression of caspase-3 may be the effects of Re and $Rk_3$ on myelosuppression.

• Journal of Periodontal and Implant Science
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• v.26 no.2
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• pp.448-468
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• 1996

To maintain its functional integrity, bone is continuously remodelled by a process involving resorption by osteoeclasts and formation by osteoblasts, In order to respond to changes in the physical environment or to trauma with the relevant action, this process is strictly regulated by locally synthesized or systemic fators, Prostaglandin $E_2(PGE_2$) is perhaps one of the best studied factors, having been known to affect bone cell function for several decades.$PGE_2$ has both anabolic and catabolic activities. Excess of $PGE_2$ has been implicated in a number of pathological states associated with bone loss in a number of chronic inflammatory conditions such as periodontal disease and rheumatoid arthritis. $PGE_2$ and other arachidonic acid metabolites have been shown to be potent stimulators of osteoclastic bone resorption in organ culture. The anabolic effects of $PGE_2$ were first noticed when an increase in periosteal woven bone formation was seen after the infusion of $PGE_2$ into infants in order to prevent closure of the ductus arteriosus. The cellular basis for the catabolic actions of $PGE_2$ has been well characterized. $PGE_2$increases osteoclast recruitment in bone marrow cell cultures. Also $PGE_2$ has a direct action on osteoclast serving to inhibit activity and can also indirectly activate osteoclast via other cells in the vicinity, presumably osteoblast. The cellular mechanisms for the anabolic actions of $PGE_2$ are not nearly so well understood. The purpose of this paper was to study the effects of $PGE_2$ and dibutyl(DB)cAMP on osteoblastic clone MC3T3El cells and on the generation of osteoclasts from their precursor cells. The effect of $PGE_2$ and DBcAMP on the induction of alkaline phoaphatase(AlP) was investigated in osteoblastic clone MC3T3El cells cultured in medium containing 0.4% fetal bovine serum. $PGE_2$ and DBcAMP stimulated ALP activity and MTT assay in the cells in a dose-dependent manner at concentrations of lO-SOOng/ml. Cycloheximide, protein synthesis inhibitor, inhibited the stimulative effect of $PGE_2$ and DBcAMP on ALP activity in the cells. $PGE_2$also increased the intracellular cAMP content in a dose-dependent fashion with a maximal effect at 500ng/ml. The effect of $PGE_2$ on the generation of osteoclasts was investigated in a coculture system of mouse bone marrow cells with primary osteoblastic cells cultured in media containing 10% fetal bovine serum.After cultures, staining for tartrate-resistant acid phosphatase(TRAP)-marker enzyme of osteoclast was performed. The TRAP(+) multinucleated cells(MNCs), which have 3 or more nuclei, were counted. More TRAP(+) MNCs were formed in coculture system than in control group. $PGE_2(10^{-5}10^{-6}M)$ stimulated the formation of osteoclast cells from mouse bone marrow cells in culture. $PGE_2(10^{-6}M)$ stimulated the formation of osteoclast cells from mouse bone marrow cells in coculture of osteoblastic clone MC3T3E1 cells This results suggest that $PGE_2$ stimulates the differentiation of osteoblasts and generation of osteoclast, and are involved in bone formation, as well as in bone resorption.

• The Korea Genome Conference
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• 2002.08a
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• pp.51-51
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• 2002

• International Journal of Oral Biology
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• v.30 no.2
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• pp.47-57
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• 2005

Leptin, the product of the obese gene, is a circulating hormone secreted primarily from adipocytes. Several results suggest that leptin is important mediators of bone metabolism. The present study was undertaken to determine the effects of leptin on anti-osteoclastogenesis using murine precursors cultured on Ca-P coated plates and on the production of osteoprotegerin (OPG) in osteoblastic cells. Additionally, this study examined the possible involvement of prostaglandin $E_2\;(PGE_2)$/protein kinase C (PKC)-mediated signals on the effect of leptin on anti-osteoclastogenesis to various culture systems of osteoclast precursors. Osteoclast generation was determined by counting tartrate-resistant acid phosphatase positive [TRAP (+)] multinucleated cells (MNCs). Osteoclastic activity was determined by measuring area of resorption pits formed by osteoclasts on Ca-P coated plate. The number of 1,25-dihydroxycholecalciferol $(1,25[OH]_2D_3)$- or $PGE_2$-induced TRAP (+) MNCs in the mouse bone marrow cell culture decreased significantly after treatment with leptin. The number of receptor activator of NF-kB ligand (RANKL)-induced TRAP (+) MNCs in M-CSF dependent bone marrow macrophage (MDBM) cell or RAW264.7 cell culture decreased significantly with leptin treatment. Indomethacin inhibited osteoclast generation induced by $1,25[OH]_2D_3$ and dexamethasone, however, no significant differences were found in the leptin treated group when compared to the corresponding indomethacin group. Phorbol 12-myristate 13-acetate (PMA), a PKC activator, inhibited osteoclast generation induced by $1,25[OH]_2D_3$. The number of TRAP (+) MNCs decreased significantly with treatment by PMA at concentrations of 0.01 and $0.1{\mu}M$ in culture. Leptin inhibited PMA-mediated osteoclast generation. Isoquinoline-5-sulfonic 2-methyl-1-piperazide dihydrochloride (H7) had no effect on osteoclast generation induced by $1,25[OH]_2D_3$. Cell culture treatment with leptin resulted in no significant differences in osteoclast generation compared to the corresponding H7 group. Indomethacin showed no significant effect on TRAP (+) MNCs formation from the RAW264.7 cell line. PMA inhibited TRAP (+) MNCs formation induced by RANKL in the RAW264.7 cell culture. H7 had no effect on osteoclast generation from the RAW264.7 cell line. There was no difference compared with the corresponding control group after treatment with leptin. $1,25[OH]_2D_3$- or $PGE_2$-induced osteoclastic activity decreased significantly with leptin treatment at a concentration of 100 ng/ml in mouse bone marrow cell culture. Indomethacin, PMA, and H7 significantly inhibited osteoclastic activity induced by $1,25[OH]_2D_3$ in mouse bone marrow cell culture. No significant differences were found between the leptin treated group and the corresponding control group. The secretion of OPG, a substance known to inhibit osteoclast formation, was detected from the osteoblasts. Treatment by leptin resulted in significant increases in OPG secretion by osteoblastic cells. Taken these results, leptin may be an important regulatory cytokines within the bone marrow microenvironment.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.47 no.2
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• pp.65-75
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• 2021

Medication-related osteonecrosis of the jaw (MRONJ) has recently associated to the increase in antiresorptive and anti-angiogenic drugs prescriptions in the treatment of oncologic and osteoporotic patients. The physiopathogenesis of MRONJ remains unclear and available treatments are unsatisfactory. Newer pharmacological treatments have shown good results, but are not curative and could have major side effects. At the same time as pharmacological treatments, mesenchymal stem cells (MSCs) have emerged as a promising therapeutic modality for tissue regeneration and repair. MSCs are multipotential non-hematopoietic progenitor cells capable to differentiating into multiple lineages of the mesenchyme. Bone marrow MSCs can differentiate into osteogenic cells and display immunological properties and secrete paracrine anti-inflammatory factors in damaged tissues. The immunomodulatory, reparative, and anti-inflammatory properties of bone marrow MSCs have been tested in a variety of animal models of MRONJ and applied in specific clinical settings. The aim of this review is to discuss critically the immunogenicity and immunomodulatory properties of MSCs, both in vitro and in vivo, the possible underlying mechanisms of their effects, and their potential clinical use as modulators of immune responses in MRONJ, and to identify clinical safety and recommendations for future research.

• Journal of Periodontal and Implant Science
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• v.35 no.2
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• pp.263-269
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• 2005

Bone morphogenetic protein(BMP) and platelet-derived growth factor(PDGF) have been demonstrated tostimulate bone formation when applied locally in vivo. To explore whether or not the combined use of BMP and PDGF could have promotive effect and synergic interaction on bone formation in vivo, bone marrow mesenchymal stem cells were treated with BMP-2, PDGF-BB, or BMP-2 plus PDGF-BB, and then these cells were injected into the subcutaneous space on the dorsum of nude mice. The bone formation was evaluated after 12 weeks. Histomorphometric analysis demonstrated that the subcutaneous nodules formed in nude mice contained 25.3% newly formed bone in the BMP-2 treated cells, 14.4% newly formed bone in the PDGF-BB treated cells, and 8.9% newly formed bone in the RMP-2 plus PDGF-BB treated cells. The results showed that the combination of BMP-2 and PDGF-BB had neither a promotive effect nor synergic interact on bone formation in vivo.

• Journal of Life Science
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• v.24 no.7
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• pp.804-811
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• 2014

A micronucleus test of cyclohexanone has not yet been conducted. To classify the chemical hazard posed by cyclohexanone according to a globally harmonized system of classification and labeling of chemicals (GHS), we investigated its mutagenicity by micronucleus induction in ICR bone marrow cells of 7-weeek-old male mice. The mice were administered three dosages of the chemical for 24 hr via the oral route. After 24 hr, the mice were sacrificed, and their bone marrow cells were prepared for smearing slides. Based on counts of micronucleated polychromatic erythrocytes (MNPCEs) of 2,000 polychromatic erythrocytes, cyclohexanone did not inhibit bone marrow cell proliferation in any of the treated groups, but it resulted in micronucleus induction. According to the results of the mammalian bone marrow micronucleus test, this chemical is mutagenic and classified as category 2 in the GHS.

• Molecules and Cells
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• v.37 no.12
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• pp.865-872
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• 2014

Premature ovarian failure (POF) is a long-term adverse effect of chemotherapy treatment. However, current available treatment regimens are not optimal. Emerging evidence suggests that bone marrow-derived mesenchymal stem cells (BMSCs) could restore the structure and function of injured tissues, but the homing and restorative effects of BMSCs on chemotherapy injured ovaries are still not clear. In this study, we found that granulosa cell (GC) apoptosis induced by cisplatin was reduced when BMSCs were migrated to granulosa cells (GCs) in vitro. Chemotherapy-induced POF was induced by intraperitoneal injection of cisplatin in rats. BMSCs labeled with enhanced green fluorescent protein (EGFP) were injected into the rats via the tail vein to investigate the homing and distribution of BMSCs in vivo. The number of BMSCs in the ovarian hilum and medulla was greater than in the cortex, but no BMSCs were found in the follicles and corpus lutea. In addition, the BMSCs treatment group's antral follicle count and estradiol levels increased after 30 days, compared with the POF group. Hence, our study demonstrates that intravenously delivered BMSCs can home to the ovaries, and restore its structure and function in POF model rats.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.6
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• pp.337-342
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• 2008

Human bone marrow mesenchymal stem cells (hBM-MSCs) represent a potentially valuable cell type for clinical therapeutic applications. The present study was designed to evaluate the effect of long-term culturing (up to $10^{th}$ passages) of hBM-MSCs from eight individual amyotrophic lateral sclerosis (ALS) patients, focusing on functional ion channels. All hBM-MSCs contain several MSCs markers with no significant differences, whereas the distribution of functional ion channels was shown to be different between cells. Four types of $K^+$ currents, including noise-like $Ca^{+2}$-activated $K^+$ current ($IK_{Ca}$), a transient outward $K^+$ current ($I_{to}$), a delayed rectifier $K^+$ current ($IK_{DR}$), and an inward-rectifier $K^+$ current ($K_{ir}$) were heterogeneously present in these cells, and a TTX-sensitive $Na^+$ current ($I_{Na,TTX}$) was also recorded. In the RT-PCR analysis, Kv1.1,, heag1, Kv4.2, Kir2.1, MaxiK, and hNE-Na were detected. In particular, ($I_{Na,TTX}$) showed a significant passage-dependent increase. This is the first report showing that functional ion channel profiling depend on the cellular passage of hBM-MSCs.

• Korean Journal of Veterinary Research
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• v.34 no.2
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• pp.237-242
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• 1994

The present study was focussed to assess the proliferating cells in the distal epiphyseal tissue of the chicken femur by immunohistochemical staining methods. Four chickens were administrated intraperitoneally by twice consecutive injections, 1 day interval with bromodeoxyuridine(Brdur, 0.05 mg/gm BW/time), and then were killed by exsanguination of jugular vein at 2 hours after last injection. Samples were taken from femur distal epiphyseas of chicken. Labeling indexes(LI) were calculated as the ratio of the number of anti-Brdur monoclonal antibody-labeled cells in the each tissue layers from basal layer of the integument to bone marrow. The overall LI were found to be $13.90{\pm}3.44%$, $30.03{\pm}7.52%$, $16.00{\pm}9.41%$, $0.00{\pm}0.00%$ and $60.03{\pm}13.39%$ at basal layer of integument, perichordrium, reseving zone in cartilage, hypertrophic zone in cartilage and bone marrow respectively. LI in proliferating zone of cartilage were found to be $36.99{\pm}7.59%$, $32.83{\pm}5.38%$ and $22.02{\pm}6.27%$ at reserving zone side region, middle region, and hypertrophic zone side region respectively. The tissue layers with higher LI were odered as bone marrow, reserving zone side region in proliferating zone, middle region in proliferating zone, perichondrium, hypertrophic zone side region in proliferating zone. reserving zone of cartilage and basal layer of integument. These data indicate that the overall LI in the each tissue layer of distal epiphyseas of the chicken femur were concluded to be higher than that in another tissue of adult birds but hypertrophic zone of cartlage were appeared to be not proliferating cells.