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  1. Article ; Online: Intramuscular injection of a plasmid DNA vector expressing hepatocyte growth factor (HGF) ameliorated pain symptoms by controlling the expression of pro-inflammatory cytokines in the dorsal root ganglion.

    Nho, Boram / Ko, Kyeong Ryang / Kim, Sunyoung / Lee, Junghun

    Biochemical and biophysical research communications

    2022  Volume 607, Page(s) 60–66

    Abstract: Hepatocyte growth factor (HGF) is a secretory protein that is involved in various biological activities such as angiogenesis, neuroprotection, and anti-inflammatory effects. Intramuscular injection of an HGF-encoding plasmid DNA (pCK-HGF-X7) has been ... ...

    Abstract Hepatocyte growth factor (HGF) is a secretory protein that is involved in various biological activities such as angiogenesis, neuroprotection, and anti-inflammatory effects. Intramuscular injection of an HGF-encoding plasmid DNA (pCK-HGF-X7) has been shown to produce pain-relieving effects in a rodent model and patients with neuropathic pain.To further investigate the underlying mechanism, we investigated the anti-inflammatory effects of HGF in the context of neuropathic pain. Consistent with previous data, intramuscular injection of pCK-HGF-X7 showed pain relieving effects up to 8 weeks and pharmacological blockade of the c-Met receptor hindered this effect, which suggest that the analgesic effect was c-Met receptor-dependent. At the histological level, macrophage infiltration in the dorsal root ganglion (DRG) was significantly decreased in the pCK-HGF-X7 injected group. Moreover, HGF treatment significantly downregulated the LPS-mediated induction of pro-inflammatory cytokines in primary cultured DRG neurons. Taken together, these data suggest that HGF-encoding plasmid DNA attenuates neuropathic pain via controlling the expression of pro-inflammatory cytokines.
    MeSH term(s) Animals ; Anti-Inflammatory Agents/metabolism ; DNA/metabolism ; Disease Models, Animal ; Ganglia, Spinal/metabolism ; Genetic Therapy ; Hepatocyte Growth Factor/metabolism ; Humans ; Injections, Intramuscular ; Neuralgia/genetics ; Neuralgia/metabolism ; Neuralgia/therapy ; Plasmids/genetics
    Chemical Substances Anti-Inflammatory Agents ; HGF protein, human ; Hepatocyte Growth Factor (67256-21-7) ; DNA (9007-49-2)
    Language English
    Publishing date 2022-03-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 205723-2
    ISSN 1090-2104 ; 0006-291X ; 0006-291X
    ISSN (online) 1090-2104 ; 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2022.03.125
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Gabapentin inhibits the analgesic effects and nerve regeneration process induced by hepatocyte growth factor (HGF) in a peripheral nerve injury model: Implication for the use of VM202 and gabapentinoids for peripheral neuropathy.

    Lee, Nayeon / Nho, Boram / Ko, Kyeong Ryang / Kim, Sunyoung / Lee, Junghun

    Molecular and cellular neurosciences

    2022  Volume 122, Page(s) 103767

    Abstract: Hepatocyte growth factor (HGF) is a multifunctional protein that plays a critical role in the angiogenic, neurotrophic, antifibrotic, and antiapoptotic activities of various cell types. It has been previously reported that intramuscular injection of pCK- ... ...

    Abstract Hepatocyte growth factor (HGF) is a multifunctional protein that plays a critical role in the angiogenic, neurotrophic, antifibrotic, and antiapoptotic activities of various cell types. It has been previously reported that intramuscular injection of pCK-HGF-X7 (or VM202), a plasmid DNA designed to express both native isoforms of human HGF (Pyun et al., 2010), significantly reduced the level of neuropathic pain in clinical studies as well as in a variety of animal models. In clinical studies, it has been observed that pCK-HGF-X7 appeared to give much higher pain-relieving effects in subjects not taking pregabalin or gabapentin, α2δ1 calcium channel blockers frequently prescribed for reducing pain in patients with diabetic peripheral neuropathy. In this study, we tested the effects of gabapentin on HGF-mediated pain reduction and nerve regeneration in vivo. Consistent with the data from clinical studies, gabapentin administration inhibited the pain reduction and axon regeneration effects mediated by HGF expression from pCK-HGF-X7. In the context of nerve regenerative effects, treatment with gabapentin or EGTA, a Ca
    MeSH term(s) Analgesics/pharmacology ; Analgesics/therapeutic use ; Animals ; Axons/metabolism ; DNA/genetics ; DNA/pharmacology ; Disease Models, Animal ; Gabapentin/pharmacology ; Gabapentin/therapeutic use ; Genetic Therapy ; Hepatocyte Growth Factor/genetics ; Hepatocyte Growth Factor/pharmacology ; Hepatocyte Growth Factor/therapeutic use ; Humans ; Nerve Regeneration ; Neuralgia/drug therapy ; Peripheral Nerve Injuries/drug therapy
    Chemical Substances Analgesics ; HGF protein, human ; Hepatocyte Growth Factor (67256-21-7) ; Gabapentin (6CW7F3G59X) ; DNA (9007-49-2)
    Language English
    Publishing date 2022-08-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1046640-x
    ISSN 1095-9327 ; 1044-7431
    ISSN (online) 1095-9327
    ISSN 1044-7431
    DOI 10.1016/j.mcn.2022.103767
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Intramuscular injection of a plasmid DNA vector expressing hepatocyte growth factor ameliorated pain symptoms by controlling the expression of pro-inflammatory cytokines in the dorsal root ganglion

    Nho, Boram / Ko, Kyeong Ryang / Kim, Sunyoung / Lee, Junghun

    Biochemical and biophysical research communications. 2022 Mar. 23,

    2022  

    Abstract: Hepatocyte growth factor (HGF) is a secretory protein that is involved in various biological activities such as angiogenesis, neuroprotection, and anti-inflammatory effects. Intramuscular injection of an HGF-encoding plasmid DNA (pCK-HGF-X7) produces ... ...

    Abstract Hepatocyte growth factor (HGF) is a secretory protein that is involved in various biological activities such as angiogenesis, neuroprotection, and anti-inflammatory effects. Intramuscular injection of an HGF-encoding plasmid DNA (pCK-HGF-X7) produces pain-relieving effects in a chronic constriction injury (CCI) neuropathic pain model. To further investigate the underlying mechanism, we investigated the anti-inflammatory effects of HGF in the context of neuropathic pain. Consistent with previous data, intramuscular injection of pCK-HGF-X7 showed pain relieving effects up to 8 weeks and pharmacological blockade of the c-Met receptor hindered this effect, which suggest that the analgesic effect was c-Met receptor dependent. At the histological level, macrophage infiltration in the dorsal root ganglion (DRG) was significantly decreased in the pCK-HGF-X7 injected group. Moreover, HGF treatment significantly downregulated the LPS-mediated induction of pro-inflammatory cytokines in primary cultured DRG neurons. Taken together, these data suggest that HGF-encoding plasmid DNA attenuates neuropathic pain via controlling the expression of pro-inflammatory cytokines.
    Keywords analgesic effect ; angiogenesis ; cytokines ; ganglia ; hepatocyte growth factor ; histology ; intramuscular injection ; macrophages ; models ; neuroprotective effect ; pain ; plasmids ; research
    Language English
    Dates of publication 2022-0323
    Publishing place Elsevier Inc.
    Document type Article
    Note Pre-press version
    ZDB-ID 205723-2
    ISSN 0006-291X ; 0006-291X
    ISSN (online) 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2022.03.125
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: Construction of Plasmid DNA Expressing Two Isoforms of Insulin-Like Growth Factor-1 and Its Effects on Skeletal Muscle Injury Models.

    Lee, Jaeman / Ko, Kyeong-Ryang / Lee, Nayeon / Kim, Sojin / Yu, Seung-Shin / Kim, Sunyoung / Lee, Junghun

    Human gene therapy

    2022  Volume 33, Issue 23-24, Page(s) 1305–1314

    Abstract: Insulin-like growth factor-1 (IGF-1) plays a significant role in the development of various organs, and several studies have suggested that IGF-1 isoforms, IGF-1 Ea and IGF-1 Ec, are expressed in skeletal muscle to control its growth. In this study, we ... ...

    Abstract Insulin-like growth factor-1 (IGF-1) plays a significant role in the development of various organs, and several studies have suggested that IGF-1 isoforms, IGF-1 Ea and IGF-1 Ec, are expressed in skeletal muscle to control its growth. In this study, we designed a novel nucleotide sequence, IGF-1-X10, consisting of IGF-1 exons and introns to simultaneously express both IGF-1 Ea and IGF-1 Ec. When transfected into human cells, the expression of both isoforms was observed at the transcript and protein levels. In an animal study, intramuscular injection of plasmid DNA comprising IGF-1-X10 induced the expression of IGF-1 Ea and IGF-1 Ec, leading to the production of functional IGF-1 protein. Finally, the efficacy of this plasmid DNA was tested in a cardiotoxin (CTX)-mediated muscle injury model and age-related muscle atrophy model. We found that IGF-1-X10 increased the muscle mass and controlled several key factors involved in the muscle atrophy program in both models. Taken together, these data suggest that IGF-1-X10 may be utilized in the form of gene therapy for the treatment of various muscle diseases related to IGF-1 deficiency.
    Language English
    Publishing date 2022-09-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1028152-6
    ISSN 1557-7422 ; 1043-0342
    ISSN (online) 1557-7422
    ISSN 1043-0342
    DOI 10.1089/hum.2022.103
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: c-Fos is necessary for HGF-mediated gene regulation and cell migration in Schwann cells.

    Ko, Kyeong Ryang / Lee, Junghun / Nho, Boram / Kim, Sunyoung

    Biochemical and biophysical research communications

    2018  Volume 503, Issue 4, Page(s) 2855–2860

    Abstract: We previously reported that the expression of hepatocyte growth factor (HGF) was highly induced after peripheral nerve damage, and that c-Fos is one of many cellular genes whose expressions are affected by the increased level of HGF[1]. c-Fos is an ... ...

    Abstract We previously reported that the expression of hepatocyte growth factor (HGF) was highly induced after peripheral nerve damage, and that c-Fos is one of many cellular genes whose expressions are affected by the increased level of HGF[1]. c-Fos is an important component of AP-1 heterodimer, but its role has not been clearly understood in the context of HGF and Schwann cells (SCs). In this study, we investigated the relationship between HGF and c-Fos. First, it was confirmed that the c-Fos was increased in SCs after nerve injury, while this effect abrogated by PHA-665752, an inhibitor of c-met receptor. When primary SCs were treated with recombinant HGF protein, c-Fos expression was regulated in a typical quick, transient fashion at both RNA and proteins levels. HGF-mediated induction of c-Fos expression was highly suppressed by specific inhibitors of ERK and CREB, respectively. The knock down of c-Fos expression by siRNA almost completely blocked various HGF-mediated effects in SCs, such as induction of gene expression of GDNF, LIF, and c-Myc, and migration of SCs, indicating that c-Fos might play a key role in HGF effects. Taken together, our results suggested that c-Fos plays a key role(s) in HGF-mediated effects on neurotrophic genes and cell migration.
    MeSH term(s) Animals ; Butadienes/pharmacology ; Cell Movement/drug effects ; Cell Movement/genetics ; Gene Expression Regulation ; Glial Cell Line-Derived Neurotrophic Factor/genetics ; Glial Cell Line-Derived Neurotrophic Factor/metabolism ; Hepatocyte Growth Factor/genetics ; Hepatocyte Growth Factor/metabolism ; Hepatocyte Growth Factor/pharmacology ; Indoles/pharmacology ; Leukemia Inhibitory Factor/genetics ; Leukemia Inhibitory Factor/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Nerve Crush/methods ; Nitriles/pharmacology ; Primary Cell Culture ; Proto-Oncogene Proteins c-fos/antagonists & inhibitors ; Proto-Oncogene Proteins c-fos/genetics ; Proto-Oncogene Proteins c-fos/metabolism ; Proto-Oncogene Proteins c-met/antagonists & inhibitors ; Proto-Oncogene Proteins c-met/genetics ; Proto-Oncogene Proteins c-met/metabolism ; Proto-Oncogene Proteins c-myc/genetics ; Proto-Oncogene Proteins c-myc/metabolism ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism ; Recombinant Proteins/pharmacology ; Schwann Cells/cytology ; Schwann Cells/drug effects ; Schwann Cells/metabolism ; Sciatic Nerve/injuries ; Sciatic Nerve/metabolism ; Signal Transduction ; Sulfones/pharmacology ; Transcription Factor AP-1/genetics ; Transcription Factor AP-1/metabolism
    Chemical Substances 5-((2,6-dichlorobenzyl)sulfonyl)-3-((3,5-dimethyl-4-((2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl)carbonyl)-1H-pyrrol-2-yl)methylene)-1,3-dihydro-2H-indol-2-one ; Butadienes ; Glial Cell Line-Derived Neurotrophic Factor ; HGF protein, mouse ; Indoles ; Leukemia Inhibitory Factor ; Lif protein, mouse ; Myc protein, mouse ; Nitriles ; Proto-Oncogene Proteins c-fos ; Proto-Oncogene Proteins c-myc ; RNA, Small Interfering ; Recombinant Proteins ; Sulfones ; Transcription Factor AP-1 ; U 0126 ; Hepatocyte Growth Factor (67256-21-7) ; Proto-Oncogene Proteins c-met (EC 2.7.10.1)
    Language English
    Publishing date 2018-08-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 205723-2
    ISSN 1090-2104 ; 0006-291X ; 0006-291X
    ISSN (online) 1090-2104 ; 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2018.08.054
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Hepatocyte Growth Factor (HGF) Promotes Peripheral Nerve Regeneration by Activating Repair Schwann Cells

    Kyeong Ryang Ko / Junghun Lee / Deokho Lee / Boram Nho / Sunyoung Kim

    Scientific Reports, Vol 8, Iss 1, Pp 1-

    2018  Volume 14

    Abstract: Abstract During the peripheral nerve regeneration process, a variety of neurotrophic factors play roles in nerve repair by acting on neuronal or non-neuronal cells. In this report, we investigated the role(s) of hepatocyte growth factor (HGF) and its ... ...

    Abstract Abstract During the peripheral nerve regeneration process, a variety of neurotrophic factors play roles in nerve repair by acting on neuronal or non-neuronal cells. In this report, we investigated the role(s) of hepatocyte growth factor (HGF) and its receptor, c-met, in peripheral nerve regeneration. When mice were subjected to sciatic nerve injury, the HGF protein level was highly increased at the injured and distal sites. The level of both total and phosphorylated c-met was also highly upregulated, but almost exclusively in Schwann cells (SCs) distal from the injury site. When mice were treated with a c-met inhibitor, PHA-665752, myelin thickness and axon regrowth were decreased indicating that re-myelination was hindered. HGF promoted the migration and proliferation of cultured SCs, and also induced the expression of various genes such as GDNF and LIF, presumably by activating ERK pathways. Furthermore, exogenous supply of HGF around the injury site, by intramuscular injection of a plasmid DNA expressing human HGF, enhanced the myelin thickness and axon diameter in injured nerves. Taken together, our results indicate that HGF and c-met play important roles in Schwann cell-mediated nerve repair, and also that HGF gene transfer may provide a useful tool for treating peripheral neuropathy.
    Keywords Medicine ; R ; Science ; Q
    Subject code 572
    Language English
    Publishing date 2018-05-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article: c-Fos is necessary for HGF-mediated gene regulation and cell migration in Schwann cells

    Ko, Kyeong Ryang / Boram Nho / Junghun Lee / Sunyoung Kim

    Biochemical and biophysical research communications. 2018 Sept. 18, v. 503, no. 4

    2018  

    Abstract: We previously reported that the expression of hepatocyte growth factor (HGF) was highly induced after peripheral nerve damage, and that c-Fos is one of many cellular genes whose expressions are affected by the increased level of HGF[1]. c-Fos is an ... ...

    Abstract We previously reported that the expression of hepatocyte growth factor (HGF) was highly induced after peripheral nerve damage, and that c-Fos is one of many cellular genes whose expressions are affected by the increased level of HGF[1]. c-Fos is an important component of AP-1 heterodimer, but its role has not been clearly understood in the context of HGF and Schwann cells (SCs). In this study, we investigated the relationship between HGF and c-Fos. First, it was confirmed that the c-Fos was increased in SCs after nerve injury, while this effect abrogated by PHA-665752, an inhibitor of c-met receptor. When primary SCs were treated with recombinant HGF protein, c-Fos expression was regulated in a typical quick, transient fashion at both RNA and proteins levels. HGF-mediated induction of c-Fos expression was highly suppressed by specific inhibitors of ERK and CREB, respectively. The knock down of c-Fos expression by siRNA almost completely blocked various HGF-mediated effects in SCs, such as induction of gene expression of GDNF, LIF, and c-Myc, and migration of SCs, indicating that c-Fos might play a key role in HGF effects. Taken together, our results suggested that c-Fos plays a key role(s) in HGF-mediated effects on neurotrophic genes and cell migration.
    Keywords cell movement ; genes ; hepatocyte growth factor ; mitogen-activated protein kinase ; nerve tissue ; Schwann cells ; small interfering RNA
    Language English
    Dates of publication 2018-0918
    Size p. 2855-2860.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 205723-2
    ISSN 0006-291X ; 0006-291X
    ISSN (online) 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2018.08.054
    Database NAL-Catalogue (AGRICOLA)

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  8. Article: Hepatocyte Growth Factor Regulates the miR-206-HDAC4 Cascade to Control Neurogenic Muscle Atrophy following Surgical Denervation in Mice.

    Choi, Wooshik / Lee, Junghun / Lee, Jaeman / Ko, Kyeong Ryang / Kim, Sunyoung

    Molecular therapy. Nucleic acids

    2018  Volume 12, Page(s) 568–577

    Abstract: Hepatocyte growth factor (HGF) has been well characterized for its roles in the migration of muscle progenitors during embryogenesis and the differentiation of muscle stem cells, but its function in adult neurogenic muscle atrophic conditions is poorly ... ...

    Abstract Hepatocyte growth factor (HGF) has been well characterized for its roles in the migration of muscle progenitors during embryogenesis and the differentiation of muscle stem cells, but its function in adult neurogenic muscle atrophic conditions is poorly understood. Here we investigated whether HGF/c-met signaling has any effects on muscle-atrophic conditions. It was found that HGF expression was upregulated in skeletal muscle tissue following surgical denervation and in hSOD1-G93A transgenic mice showing severe muscle loss. Pharmacological inhibition of the c-met receptor decreased the expression level of pri-miR-206, enhanced that of HDAC4 and atrogenes, and resulted in increased muscle atrophy. In C2C12 cells, HGF inhibited phosphorylation of Smad3 and relieved TGF-β-mediated suppression of miR-206 expression via JNK. When extra HGF was exogenously provided through intramuscular injection of plasmid DNA expressing HGF, the extent of muscle atrophy was reduced, and the levels of all affected biochemical markers were changed accordingly, including those of primary and mature miR-206, HDAC4, and various atrogenes. Taken together, our finding suggested that HGF might play an important role in regard to neurogenic muscle atrophy and that HGF might be used as a platform to develop therapeutic agents for neuromuscular disorders.
    Language English
    Publishing date 2018-07-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2662631-7
    ISSN 2162-2531
    ISSN 2162-2531
    DOI 10.1016/j.omtn.2018.06.013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Hepatocyte Growth Factor (HGF) Promotes Peripheral Nerve Regeneration by Activating Repair Schwann Cells.

    Ko, Kyeong Ryang / Lee, Junghun / Lee, Deokho / Nho, Boram / Kim, Sunyoung

    Scientific reports

    2018  Volume 8, Issue 1, Page(s) 8316

    Abstract: During the peripheral nerve regeneration process, a variety of neurotrophic factors play roles in nerve repair by acting on neuronal or non-neuronal cells. In this report, we investigated the role(s) of hepatocyte growth factor (HGF) and its receptor, c- ... ...

    Abstract During the peripheral nerve regeneration process, a variety of neurotrophic factors play roles in nerve repair by acting on neuronal or non-neuronal cells. In this report, we investigated the role(s) of hepatocyte growth factor (HGF) and its receptor, c-met, in peripheral nerve regeneration. When mice were subjected to sciatic nerve injury, the HGF protein level was highly increased at the injured and distal sites. The level of both total and phosphorylated c-met was also highly upregulated, but almost exclusively in Schwann cells (SCs) distal from the injury site. When mice were treated with a c-met inhibitor, PHA-665752, myelin thickness and axon regrowth were decreased indicating that re-myelination was hindered. HGF promoted the migration and proliferation of cultured SCs, and also induced the expression of various genes such as GDNF and LIF, presumably by activating ERK pathways. Furthermore, exogenous supply of HGF around the injury site, by intramuscular injection of a plasmid DNA expressing human HGF, enhanced the myelin thickness and axon diameter in injured nerves. Taken together, our results indicate that HGF and c-met play important roles in Schwann cell-mediated nerve repair, and also that HGF gene transfer may provide a useful tool for treating peripheral neuropathy.
    MeSH term(s) Animals ; Cell Proliferation ; Hepatocyte Growth Factor/physiology ; Mice ; Myelin Sheath/metabolism ; Nerve Regeneration ; Peripheral Nerves/metabolism ; Peripheral Nerves/physiology ; Phosphorylation ; Schwann Cells/cytology
    Chemical Substances Hepatocyte Growth Factor (67256-21-7)
    Language English
    Publishing date 2018-05-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-018-26704-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Dehydrodiconiferyl alcohol promotes BMP-2-induced osteoblastogenesis through its agonistic effects on estrogen receptor.

    Lee, Wonwoo / Ko, Kyeong Ryang / Kim, Hyun-Keun / Lim, Seonung / Kim, Sunyoung

    Biochemical and biophysical research communications

    2018  Volume 495, Issue 3, Page(s) 2242–2248

    Abstract: Estrogen deficiency results in an imbalance between the levels of bone-resorping osteoclasts and bone-forming osteoblasts, eventually leading to overall bone loss. Dehydrodiconiferyl alcohol (DHCA), a lignan compound originally isolated from Cucurbita ... ...

    Abstract Estrogen deficiency results in an imbalance between the levels of bone-resorping osteoclasts and bone-forming osteoblasts, eventually leading to overall bone loss. Dehydrodiconiferyl alcohol (DHCA), a lignan compound originally isolated from Cucurbita moschata, has been shown to bind to estrogen receptor, and indeed exhibits various activities of estrogen, such as anti-inflammatory and anti-oxidative stress effects. In this study, we tested whether synthetic DHCA could affect the BMP-2-induced osteoblastogenesis in vitro. In MC3T3-E1 cells, DHCA promoted BMP-2-induced differentiation of osteoblasts. Consistently, the expression of three osteoblastogenic genes known to be induced by BMP-2, ALP, osteocalcin and OPG, was up-regulated by DHCA treatment. DHCA was also shown to activate the production of RUNX2 by activating Smad1/5/9 and AMPK. Data from transient transfection assays suggested that DHCA might activate the estrogen receptor signaling pathway. Effects of DHCA on BMP-2-induced osteoblastogenesis were reduced when cells were treated with a specific siRNA to ERα or ERβ. Taken together, our results suggest that DHCA may be developed as an efficient therapeutic for osteoporosis by regulating osteoblastogenesis through its estrogenic effects.
    MeSH term(s) 3T3 Cells ; Animals ; Bone Morphogenetic Protein 2/metabolism ; Cell Differentiation/drug effects ; Cell Differentiation/physiology ; Dose-Response Relationship, Drug ; Estrogen Receptor Modulators/administration & dosage ; Estrogens/metabolism ; Mice ; Osteoblasts/cytology ; Osteoblasts/drug effects ; Osteoblasts/physiology ; Osteogenesis/drug effects ; Osteogenesis/physiology ; Phenols/administration & dosage ; Receptors, Estrogen/drug effects ; Receptors, Estrogen/metabolism
    Chemical Substances Bmp2 protein, mouse ; Bone Morphogenetic Protein 2 ; Estrogen Receptor Modulators ; Estrogens ; Phenols ; Receptors, Estrogen ; dehydrodiconiferyl alcohol (4263-87-0)
    Language English
    Publishing date 2018--15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 205723-2
    ISSN 1090-2104 ; 0006-291X ; 0006-291X
    ISSN (online) 1090-2104 ; 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2017.12.079
    Database MEDical Literature Analysis and Retrieval System OnLINE

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