Woo Youl Kang
Kyungpook National University
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Featured researches published by Woo Youl Kang.
Journal of Cellular Physiology | 2016
Hyun-Ju Kim; Hye-Jin Yoon; Bo Kyung Kim; Woo Youl Kang; Sook Jin Seong; Mi-Sun Lim; Shin-Yoon Kim; Young-Ran Yoon
G protein‐coupled receptor 120 (GPR120) plays an important role in the regulation of inflammation and lipid metabolism. In this study, we investigated the role of GPR120 in osteoclast development and found that GPR120 regulates osteoclast differentiation, survival and function. We observed that GPR120 was highly expressed in osteoclasts compared to their precursors, bone marrow‐derived macrophages (BMMs). Activation of GPR120 by its ligand GW9508 suppressed receptor activator of NF‐ κB ligand (RANKL)‐induced osteoclast differentiation and the expression of nuclear factor of activated T cells c1 (NFATc1), a key modulator of osteoclastogenesis. GPR120 activation further inhibited the RANKL‐stimulated phosphorylation of IκBα and JNK. In addition to osteoclast differentiation, GPR120 activation increased the apoptosis of mature osteoclasts by inducing caspase‐3 and Bim expression. Activation of GPR120 also interfered with cell spreading and actin cytoskeletal organization mediated by M‐CSF but not by RANKL. Coincident with the impaired cytoskeletal organization, GPR120 activation blocked osteoclast bone resorbing activity. Furthermore, knockdown of GPR120 using small hairpin RNA abrogated all these inhibitory effects on osteoclast differentiation, survival, and function. Together, our findings identify GPR120 as a negative modulator of osteoclast development that may be an attractive therapeutic target for bone‐destructive diseases. J. Cell. Physiol. 231: 844–851, 2016.
Cellular Signalling | 2017
Hyun-Ju Kim; Boram Ohk; Hye Jin Yoon; Woo Youl Kang; Sook Jin Seong; Shin-Yoon Kim; Young-Ran Yoon
Docosahexaenoic acid (DHA), a component of omega-3 fatty acids, has been reported to protect against inflammatory bone diseases such as osteoporosis and rheumatoid arthritis. However, its exact mechanism in bone resorbing cells has not been elucidated. In this study, we investigated the effects and the molecular mechanism of DHA on the proliferation, differentiation, and survival of osteoclast lineage cells using mouse bone marrow-derived macrophages (BMMs). DHA suppressed the macrophage colony-stimulating factor (M-CSF)-induced proliferation of osteoclast precursors, BMMs, in a dose-dependent manner. The attenuated proliferation of DHA-treated BMMs was related to M-CSF inhibition that selectively decreased Akt activation and downregulated cyclin D1 and cyclin D2 expression. DHA also blocked receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation from BMMs. At the molecular level, DHA inhibited JNK, ERK, and p38 MAPKs. In addition, it inhibited NF-κB signaling cascades, as demonstrated by the suppression of RANKL-mediated IκBα phosphorylation, NF-κB subunit p65 nuclear translocation, and NF-κB transcriptional activation. Accordingly, DHA attenuated the induction of c-Fos and nuclear factor of activated T cells c1 (NFATc1). Furthermore, DHA accelerated the apoptosis of mature osteoclasts by inducing Bim expression, a critical modulator of osteoclast apoptosis. Collectively, our data demonstrate that DHA exerts an anti-osteoclastogenic effect by suppressing the proliferation and differentiation of BMMs and enhancing the apoptosis of mature osteoclasts, thereby resulting in a diminished number of bone-resorptive cells.
Journal of Bone Metabolism | 2016
Hyun Ju Kim; Boram Ohk; Woo Youl Kang; Sook Jin Seong; Kyoungho Suk; Mi Sun Lim; Shin Yoon Kim; Young Ran Yoon
Background Lipocalin-2 (LCN2), a small glycoprotein, has a pivotal role in diverse biological processes such as cellular proliferation and differentiation. We previously reported that LCN2 is implicated in osteoclast formation induced by receptor activator of nuclear factor-kappa B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). In the present study, we used a knockout mouse model to further investigate the role of LCN2 in osteoclast development. Methods Osteoclastogenesis was assessed using primary bone marrow-derived macrophages. RANKL and M-CSF signaling was determined by immunoblotting, cell proliferation by bromodeoxyuridine (BrdU) enzyme-linked immunosorbent assay (ELISA), and apoptosis by cell death detection ELISA. Bone morphometric parameters were determined using a micro-computed tomography system. Results Our results showed that LCN2 deficiency increases tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclast formation in vitro, a finding that reflects enhanced proliferation and differentiation of osteoclast lineage cells. LCN2 deficiency promotes M-CSF-induced proliferation of bone marrow macrophages (BMMs), osteoclast precursors, without altering their survival. The accelerated proliferation of LCN2-deficient precursors is associated with enhanced expression and activation of the M-CSF receptor, c-Fms. Furthermore, LCN2 deficiency stimulates the induction of c-Fos and nuclear factor of activated T cells c1 (NFATc1), key transcription factors for osteoclastogenesis, and promotes RANKL-induced inhibitor of kappa B (IκBα) phosphorylation. Interestingly, LCN2 deficiency does not affect basal osteoclast formation in vivo, suggesting that LCN2 might play a role in the enhanced osteoclast development that occurs under some pathological conditions. Conclusions Our study establishes LCN2 as a negative modulator of osteoclast formation, results that are in accordance with our previous findings.
Cellular Signalling | 2016
Hyun-Ju Kim; Woo Youl Kang; Sook Jin Seong; Shin-Yoon Kim; Mi-Sun Lim; Young-Ran Yoon
Follistatin-like 1 (FSTL1) functions as a pivotal modulator of inflammation and is implicated in many inflammatory diseases such as rheumatoid arthritis. Here, we report that FSTL1 is strongly upregulated and secreted during osteoclast differentiation of bone marrow-derived macrophages (BMMs) and that FSTL1 positively regulates osteoclast formation induced by RANKL and M-CSF. The overexpression of FSTL1 or treatment with recombinant FSTL1 (rFSTL1) in BMMs enhances the formation of multinuclear osteoclasts and the induction of c-Fos and NFATc1, transcription factors important for osteoclastogenesis. Conversely, knockdown of FSTL1 using a small hairpin RNA suppresses osteoclast formation and the expression of these transcription factors. While FSTL1 does not affect RANKL-stimulated activation of p38 MAPK, phosphorylation of IκBα, JNK, and ERK were increased by overexpression or addition of rFSTL1. Furthermore, rFSTL1 increased RANKL-induced NF-κB transcriptional activity in a dose-dependent manner. In addition to its role in osteoclastogenesis, FSTL1 promotes proliferation of osteoclast precursors by increasing M-CSF-induced ERK activation, which in turn leads to accelerated osteoclast formation. Together, our findings demonstrate that FSTL1 is a secreted osteoclastogenic factor that plays a critical role in osteoclast formation via the NF-κB and MAPKs signaling pathways.
Experimental Cell Research | 2017
Chae-Eun Yeo; Woo Youl Kang; Sook Jin Seong; Seung Il Cho; Hae Won Lee; Young-Ran Yoon; Hyun-Ju Kim
&NA; Neuromedin B (NMB), a mammalian bombesin‐like peptide, regulates diverse physiological processes, such as energy metabolism, memory and fear behavior, and cellular growth, through its cognate receptor, NMBR. In this study, we report that NMB expression was upregulated during osteoclast development and that silencing NMB or NMBR attenuated osteoclast generation mediated by macrophage colony‐stimulating factor (M‐CSF) and receptor activator of NF‐&kgr;B ligand (RANKL). We found that knockdown of NMB or NMBR using a small hairpin RNA suppressed M‐CSF‐induced proliferation of osteoclast precursor cells without altering osteoclast differentiation. Interestingly, NMB or NMBR knockdown reduced the expression of the M‐CSF receptor, c‐Fms, which is an important modulator of osteoclast development. Consequently, NMB or NMBR silencing inhibited M‐CSF/c‐Fms‐mediated downstream signaling pathways like activation of ERK and Akt and induction of D‐type cyclins, cyclin D1 and D2. Moreover, knockdown of NMB or NMBR accelerated apoptosis in osteoclast lineage cells by inducing caspase‐3, caspase‐9, and Bim expression. In summary, our study demonstrates that the NMB/NMBR axis plays a pivotal role in osteoclast generation by modulating the proliferation and survival of osteoclast lineage cells. HighlightsNMB and NMBR expression is regulated during osteoclast development.NMB/NMBR axis regulates osteoclast generation mediated by M‐CSF and RANKL.NMB/NMBR silencing suppresses M‐CSF‐induced osteoclast precursor proliferation.NMB/NMBR silencing accelerates apoptosis in osteoclast lineage cells.
Journal of Cellular Physiology | 2018
Ji-Wan Park; Hye-Jin Yoon; Woo Youl Kang; Seung Il Cho; Sook Jin Seong; Hae Won Lee; Young-Ran Yoon; Hyun-Ju Kim
GPR84, a member of the G protein‐coupled receptor family, is found predominantly in immune cells, such as macrophages, and functions as a pivotal modulator of inflammatory responses. In this study, we investigated the role of GPR84 in receptor activator of nuclear factor‐κB ligand (RANKL)‐induced osteoclast differentiation. Our microarray data showed that GPR84 was significantly downregulated in osteoclasts compared to in their precursors, macrophages. The overexpression of GPR84 in bone marrow‐derived macrophages suppressed the formation of multinucleated osteoclasts without affecting precursor proliferation. In addition, GPR84 overexpression attenuated the induction of c‐Fos and nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), which are transcription factors that are critical for osteoclastogenesis. Furthermore, knockdown of GPR84 using a small hairpin RNA promoted RANKL‐mediated osteoclast differentiation and gene expression of osteoclastogenic markers. Mechanistically, GPR84 overexpression blocked RANKL‐stimulated phosphorylation of IκBα and three MAPKs, JNK, ERK, and p38. GPR84 also suppressed NF‐κB transcriptional activity mediated by RANKL. Conversely, GPR84 knockdown enhanced RANKL‐induced activation of IκBα and the three MAPKs. Collectively, our results revealed that GPR84 functions as a negative regulator of osteoclastogenesis, suggesting that it may be a potential therapeutic target for osteoclast‐mediated bone‐destructive diseases.
Journal of Ginseng Research | 2018
Min-Koo Choi; Sojeong Jin; Ji-Hyeon Jeon; Woo Youl Kang; Sook Jin Seong; Young-Ran Yoon; Yong-Hae Han; Im-Sook Song
Background We investigated the tolerability and pharmacokinetic properties of various ginsenosides, including Rb1, Rb2, Rc, Rd, and compound K, after single or multiple administrations of red ginseng extract in human beings. Methods Red ginseng extract (dried ginseng > 60%) was administered once and repeatedly for 15 days to 15 healthy Korean people. After single and repeated administration of red ginsengextract, blood sample collection, measurement of blood pressure and body temperature, and routine laboratory test were conducted over 48-h test periods. Results Repeated administration of high-dose red ginseng for 15 days was well tolerated and did not produce significant changes in body temperature or blood pressure. The plasma concentrations of Rb1, Rb2, and Rc were stable and showed similar area under the plasma concentration-time curve (AUC) values after 15 days of repeated administration. Their AUC values after repeated administration of red ginseng extract for 15 days accumulated 4.5- to 6.7-fold compared with single-dose AUC. However, the plasma concentrations of Rd and compound K showed large interindividual variations but correlated well between AUC of Rd and compound K. Compound K did not accumulate after 15 days of repeated administration of red ginseng extract. Conclusion A good correlation between the AUC values of Rd and compound K might be the result of intestinal biotransformation of Rb1, Rb2, and Rc to Rd and subsequently to compound K, rather than the intestinal permeability of these ginsenosides. A strategy to increase biotransformation or reduce metabolic intersubject variability may increase the plasma concentrations of Rd and compound K.
Drug Design Development and Therapy | 2018
Woo Youl Kang; Sook Jin Seong; Boram Ohk; Mi-Ri Gwon; Bo Kyung Kim; Sookie La; Hyun-Ju Kim; Seung Il Cho; Young-Ran Yoon; Dong Heon Yang; Hae Won Lee
Purpose A new fixed-dose combination (FDC) formulation of telmisartan 80 mg and S-amlodipine 5 mg (CKD-828) has been developed to increase convenience (as only one tablet is required per day) and improve treatment compliance. Methods The pharmacokinetic characteristics and tolerability of an FDC of telmisartan and S-amlodipine were compared to those after coadministration of the individual agents in this randomized, open-label, single-dose, two-way, four-period, crossover study. To analyze the telmisartan and S-amlodipine plasma concentrations using a validated liquid chromatography–tandem mass spectrometry method, serial blood samples were collected up to 48 hours post-dose for telmisartan and 144 hours post-dose for S-amlodipine, in each period. Results Forty-eight healthy subjects were enrolled, and 43 completed the study. The mean peak plasma concentration (Cmax) and the area under the plasma concentration–time curve from time 0 to the last measurement (AUC0–t) values of telmisartan were 522.29 ng/mL and 2,475.16 ng·h/mL for the FDC, and 540.45 ng/mL and 2,559.57 ng·h/mL for the individual agents concomitantly administered, respectively. The mean Cmax and AUC0–t values of S-amlodipine were 2.71 ng/mL and 130.69 ng·h/mL for the FDC, and 2.74 ng/mL and 129.81 ng·h/mL for the individual agents concomitantly administered, respectively. The geometric mean ratio (GMR) and 90% confidence interval (CI) for the telmisartan Cmax and AUC0–t (FDC of telmisartan and S-amlodipine/concomitant administration) were 0.8509 (0.7353–0.9846) and 0.9431 (0.8698–1.0226), respectively. The GMR and 90% CI for the S-amlodipine Cmax and AUC0–t (FDC/concomitant administration) were 0.9829 (0.9143–1.0567) and 0.9632 (0.8798–1.0546), respectively. As the intrasubject variability of the Cmax for telmisartan administered individually was 42.94%, all 90% CIs of the GMRs fell within the predetermined acceptance range. Both treatments were well tolerated in this study. Conclusion CKD-828 FDC tablets were shown to be bioequivalent to coadministration of the individual agents with the respective strength, in healthy subjects under fasting conditions. There was no significant difference in safety profile between the two treatments.
Clinical Therapeutics | 2018
Sook Jin Seong; Woo Youl Kang; Jae-Kyung Heo; Jungjae Jo; Won Gu Choi; Kwang-Hyeon Liu; Sangkyu Lee; Min-Koo Choi; Yong-Hae Han; Hye Suk Lee; Boram Ohk; Hae Won Lee; Im-Sook Song; Young-Ran Yoon
Purpose: Red ginseng is one of the worlds most popular herbal medicines; it exhibits a wide range of pharmacologic activities and is often co-ingested with other herbal and conventional medicines. This open-label, randomized, 3-period study investigated the in vivo herb-drug interaction potential for red ginseng extract with cytochrome P-450 (CYP) enzymes and organic anion-transporting polypeptide (OATP) 1B1. METHODS Fifteen healthy male volunteers (22-28 years; 57.1-80.8 kg) were administered a single dose of cocktail probe substrates (caffeine 100 mg, losartan 50 mg, omeprazole 20 mg, dextromethorphan 30 mg, midazolam 2 mg, and pitavastatin 2 mg) and single or multiple doses of red ginseng extract for 15 days. FINDINGS The pharmacokinetic profiles of the probe substrates and metabolites after single- or multiple-dose administration of red ginseng extracts were comparable to the corresponding profiles of the control group. The geometric mean ratio of AUC0-t and 90% CIs for the probe substrate drugs between the control and multiple doses of red ginseng for 15 days were within 0.8 to 1.25 (CYP2C9, CYP3A4, and OATP1B1 probe substrates) or slightly higher (CYP1A2, CYP2C19, and CYP2D6 probe substrates). Additional assessments of the in vitro drug interaction potential of red ginseng extracts and the ginsenoside Rb1 on drug-metabolizing enzymes and transporters using human liver microsomes, cryopreserved human hepatocytes, and transporter-overexpressed cells were negative. IMPLICATIONS Red ginseng poses minimal risks for clinically relevant CYP- or OATP-mediated drug interactions and is well tolerated. Clinical Research Information Service registry no.
Translational and Clinical Pharmacology | 2017
Seung Il Cho; Moonyoung Jegal; Boram Ohk; Bo Kyung Kim; Mi-Ri Gwon; Woo Youl Kang; Sook Jin Seong; Hyun-Ju Kim; Hae Won Lee; Young-Ran Yoon
This study describes the development of an analytical method to determine sumatriptan levels in human plasma using high performance liquid chromatography (HPLC) coupled with triple quadrupole tandem mass spectrometry (MS/MS) and its application to a pharmacokinetic study in healthy Korean volunteers. A single 50 mg dose of sumatriptan was orally administered to twelve healthy volunteers (nine women and three men). The HPLC-MS/MS analytical method was validated with respect to its specificity, linearity, sensitivity, accuracy, precision, recovery, and stability. The calibration curve was linear over a concentration range of 0.3–100 ng/mL (r > 0.999). The lower limit of quantitation for sumatriptan in plasma was 0.3 ng/mL. The accuracy and precision of the analytical method were acceptable within 15% at all quality control levels. We compared plasma concentration-time curves as well as pharmacokinetic parameters such as the area under the curve (AUC) and maximum plasma concentration (Cmax). Both the mean AUC and Cmax of sumatriptan were 1.56 times higher in women than in men. These differences could be largely explained by the difference in body weight (44%) between women and men. The outcomes may provide insights into developing appropriate individualized treatment strategies.