22 results match your criteria: "Joint Center for Biosciences[Affiliation]"

Bone morphogenic protein 9 is a novel thermogenic hepatokine secreted in response to cold exposure.

Metabolism

April 2022

Korea Mouse Metabolic Phenotyping Center, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea; Division of Molecular Medicine, Department of Medicine, Gachon University College of Medicine, Incheon 21565, Republic of Korea; Endocrinology, Internal Medicine, Gachon University Gil Medical Center, Incheon 21565, Republic of Korea. Electronic address:

Objective: Maintaining a constant core body temperature is essential to homeothermic vertebrate survival. Adaptive thermogenesis in brown adipose tissue and skeletal muscle is the primary mechanism of adjustment to an external stimulus such as cold exposure. Recently, several reports have revealed that the liver can play a role as a metabolic hub during adaptive thermogenesis.

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Design-augmented (DA) biologics: BMP chimeras for bone and cartilage regeneration.

Osteoarthritis Cartilage

February 2020

Qualcomm Institute, University of California San Diego, Atkinson Hall - Fifth Floor, 9500 Gilman Drive #0436, La Jolla, CA 92093-0436, USA; Protein Engineering Laboratory, Joint Center for Biosciences, Songdo Smart Valley, Yeonsu-gu, Incheon, 406-840, USA. Electronic address:

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Objective: To compare the spinal bone fusion properties of activin A/BMP2 chimera (AB204) with recombinant human bone morphogenetic protein (rhBMP2) using a rat posterolateral spinal fusion model.

Methods: The study was designed to compare the effects and property at different dosages of AB204 and rhBMP2 on spinal bone fusion. Sixty-one male Sprague-Dawley rats underwent posterolateral lumbar spinal fusion using one of nine treatments during the study, that is, sham; osteon only; 3.

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The Cardiovascular Effect of Single Injection and Toxicologic Effects of Repetitive 2-Week Intravenous Administration of Activin A/BMP-2 Chimera in Beagle Dog.

Cardiovasc Toxicol

February 2018

Department of Orthopedic Surgery, Seoul National University, College of Medicine, 101, Daehak-ro, Jongno-gu, Seoul, 03080, Korea.

This study was performed for the purpose to evaluate the effect of activin A/BMP-2 chimera (AB204) on cardiovascular system and toxicological effect in beagle dogs. When administered AB204 at the dose of 0.32 mg/kg via intravenous injection in beagle dogs, there were no changes in systolic, diastolic and mean blood pressure as well as in pulse rate, in addition that there were no differences in ORS complex, PR interval, R-R interval, QT interval and QTcV interval on the electrocardiography.

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The biological role of BMP-9 signaling in liver cancer remains dubious. To explore the potential use of BMP-9 signaling for anti-cancer therapy, we used recombinant human BMP-9, which we referred to as MB109, to study the effect on growth of fifteen hepatocellular carcinoma (HCC) cell lines. MB109 effectively inhibits the proliferation of nine HCC cells in vitro.

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BMP-9 enhances fibroblast growth factor 21 expression and suppresses obesity.

Biochim Biophys Acta

July 2016

Laboratory of Drugs to Medicine, Joint Center for Biosciences, Incheon 406-840, South Korea. Electronic address:

Although BMP-9 has been reported to induce browning of white adipose tissues (WATs) and suppress high fat diet-induced obesity, detailed molecular mechanism needs to be further elucidated. We report here that administration of MB109, a recombinant derivative of human BMP-9, into obese mice enhanced gene expression of fibroblast growth factor 21 (FGF21), a metabolic regulator, and alleviates a spectrum of pathological symptoms due to high fat diet-induced obesity. In addition, periodical injection of MB109 (500μg/kg/week) reduced an amount of lipid droplets in the liver, serum levels of alanine aminotransferase (ALT), and total cholesterol.

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The purpose of this study was to determine the effects of a single intravenous injection of a novel osteoinductive material, activin A/BMP-2 (AB204), to rodents on toxicity and their respiratory functions and central nervous system (CNS). A single intravenous injection of AB204 was given to Sprague-Dawley (SD) rats in doses of 0, 0.625, 2.

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The toxicological evaluation of repetitive 2- and 4-week intravenous injection of Activin A/BMP-2 chimera (AB204) into rats.

Regul Toxicol Pharmacol

October 2015

Protein Engineering Laboratory, Joint Center for Biosciences at Songdo Smart Valley, Incheon 406-840, Republic of Korea; Structural Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.

The subchronic (28-days) toxicity of an Activin A/BMP-2 chimera (AB204) was assessed in rats. Sprague-Dawley rats received repetitive intravenous injection of AB204 in doses of 0, 0.25 and 0.

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Biphasic effects of FGF2 on adipogenesis.

PLoS One

February 2016

Laboratory of Genome to Drug Medicine, joint Center for Biosciences, Incheon, Korea.

Although stem cells from mice deficient of FGF2 have been reported to display enhanced capacity for adipogenesis, the literature using in vitro cell culture system has so far reported conflicting results on the role of FGF2 in adipogenesis. We here demonstrate that FGF2, depending on concentration, can function as either a positive or negative factor of in vitro adipogenesis by regulating activation of the ERK signaling pathway. FGF2 at concentrations lower than 2 ng/ml enhanced in vitro adipogenesis of human adipose-derived stem cells (hASCs).

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Engineering TGF-β superfamily ligands for clinical applications.

Trends Pharmacol Sci

December 2014

Structural Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Drug Discovery Collaboratory, Joint Center for Biosciences, Incheon 406-840, Korea. Electronic address:

TGF-β superfamily ligands govern normal tissue development and homeostasis, and their dysfunction is a hallmark of many diseases. These ligands are also well defined both structurally and functionally. This review focuses on TGF-β superfamily ligand engineering for therapeutic purposes, in particular for regenerative medicine and musculoskeletal disorders.

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Background: One in eight women will be affected by breast cancer in her lifetime. Approximately 75% of breast cancers express estrogen receptor alpha (ERα) and/or progesterone receptor and these receptors are markers for tumor dependence on estrogen. Anti-estrogenic drugs such as tamoxifen are commonly used to block estrogen-mediated signaling in breast cancer.

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Abnormal degradation of matrix components due to dysregulated expression of matrix metalloproteinase (MMP)-9 in macrophages has been linked to progression of acute cerebral ischemia and atherosclerosis. We report that lithium chloride (LiCl) or CHIR99021, inhibitors of Wnt signaling pathway, enhance phosphorylation of glycogen synthase kinase-3beta and suppress lipopolysaccharide-mediated upregulation of MMP-9 expression in murine macrophage RAW264.7 cells in a dose-dependent manner.

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An activin A/BMP2 chimera, AB204, displays bone-healing properties superior to those of BMP2.

J Bone Miner Res

September 2014

Protein Engineering Laboratory, Joint Center for Biosciences at Songdo Global University Campus, Incheon, Republic of Korea; Department of Pharmacology, Seoul National University College of Medicine, Seoul, Republic of Korea.

Recombinant bone morphogenetic protein 2 (rhBMP2) has been used clinically to treat bone fractures in human patients. However, the high doses of rhBMP2 required for a therapeutic response can cause undesirable side effects. Here, we demonstrate that a novel Activin A/BMP2 (AB2) chimera, AB204, promotes osteogenesis and bone healing much more potently and effectively than rhBMP2.

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MB109 as bioactive human bone morphogenetic protein-9 refolded and purified from E. coli inclusion bodies.

Microb Cell Fact

February 2014

Protein Engineering Laboratory, joint Center for Biosciences, Songdo Smart Valley, 214 Sondgo-dong, Yeonsu-gu, Incheon 406-840, Korea.

Background: The development of chemical refolding of transforming growth factor-beta (TGF-β) superfamily ligands has been instrumental to produce the recombinant proteins for biochemical studies and exploring the potential of protein therapeutics. The osteogenic human bone morphogenetic protein-2 (hBMP-2) and its Drosophila DPP homolog were the early successful cases of refolding into functional form. Despite the similarity in their three dimensional structure and amino acid sequences, several other TGF-β superfamily ligands could not be refolded readily by the same methods.

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Drug screening strategy for human membrane proteins: from NMR protein backbone structure to in silica- and NMR-screened hits.

Biochem Biophys Res Commun

March 2014

Structural Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Rd., La Jolla, CA 92037, USA; Joint Center for Biosciences, 301-B, Songdo Smart Valley 214, Songdo-dong, Yeonsu-ku, Incheon 406-840, Republic of Korea; Drug Discovery Collaboratory, Carlsbad, CA 92008, USA. Electronic address:

About 8000 genes encode membrane proteins in the human genome. The information about their druggability will be very useful to facilitate drug discovery and development. The main problem, however, consists of limited structural and functional information about these proteins because they are difficult to produce biochemically and to study.

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BMP-9 as a potent brown adipogenic inducer with anti-obesity capacity.

Biomaterials

March 2014

Laboratory of Genome to Drug Medicine, Joint Center for Biosciences, Incheon 406-840, Republic of Korea. Electronic address:

BMP-9, whose expression is highest in liver cells, has been demonstrated to regulate expression of enzymes involved in glucose homeostasis. However, the underlying mechanism of this effect has yet to be elucidated. We observed that MB109, a recombinant BMP-9 derivative, enhanced brown adipogenesis of human adipose tissue derived stem cells.

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Bone morphogenetic proteins (BMPs) have diverse and important roles in the proliferation and differentiation of adult stem cells in our tissues. Especially, BMPs are well known to be the main inducers of bone formation, by facilitating both proliferation and differentiation of bone stem cells. Interestingly, in skin stem cells, BMPs repress their proliferation but are indispensable for the proper differentiation into several lineages of skin cells.

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Although both glucose deprivation and hypoxia have been reported to promote cascades of biological alterations that lead to induction of inflammatory mediators, we hypothesized that glucose deprivation and hypoxia might show neutral, synergistic or antagonistic effects to each other on gene expression of inflammatory mediators depending on the regulatory components in their promoters. Gene expression of interleukin 6 (IL-6) was analyzed by real-time PCR, ELISA, or Western blot. Effects of glucose deprivation and/or hypoxia on activation of signaling pathways were analyzed by time-dependent phosphorylation patterns of signaling molecules.

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Statins suppress expression of pro-inflammatory cytokines in endothelial cells, whereas they enhance it in immune cells. Pro-inflammatory cytokines and lipopolysaccharide (LPS) induce matrix metalloproteinase (MMP)-9 gene expression in macrophages, which has been linked to progress of various inflammatory diseases. The aim of this study was to identify effects of various statins on LPS-induced MMP-9 gene expression in macrophages and microglia.

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Transforming Growth Factor--beta (TGFβ) superfamily ligands, including Activins, Growth and Differentiation Factors (GDFs), and Bone Morphogenetic Proteins (BMPs), are excellent targets for protein-based therapeutics because of their pervasiveness in numerous developmental and cellular processes. We developed a strategy termed RASCH (Random Assembly of Segmental Chimera and Heteromer), to engineer chemically-refoldable TGFβ superfamily ligands with unique signaling properties. One of these engineered ligands, AB208, created from Activin-βA and BMP-2 sequences, exhibits the refolding characteristics of BMP-2 while possessing Activin-like signaling attributes.

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BMPs and their clinical potentials.

BMB Rep

October 2011

Joint Center for Biosciences at Lee Gil Ya Cancer and Diabetes Research Institute, Gachon University of Medicine and Science, IncheonKorea.

Bone morphogenetic protein (BMP) signaling in diseases is the subject of an overwhelming array of studies. BMPs are excellent targets for treatment of various clinical disorders. Several BMPs have already been shown to be clinically beneficial in the treatment of a variety of conditions, including BMP-2 and BMP-7 that have been approved for clinical application in nonunion bone fractures and spinal fusions.

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Transgenic microalgae expressing Escherichia coli AppA phytase as feed additive to reduce phytate excretion in the manure of young broiler chicks.

Appl Microbiol Biotechnol

August 2011

Protein Engineering Laboratory, Joint Center for Biosciences at LCDI, Gachon University of Medicine and Science, 7-45 Songdo-dong, Yeonsu-ku, Incheon 406-840, South Korea.

Microbial phytases are widely used as feed additive to increase phytate phosphorus utilization and to reduce fecal phytates and inorganic phosphate (iP) outputs. To facilitate the process of application, we engineered an Escherichia coli appA phytase gene into the chloroplast genome of the model microalga, Chlamydomonas reinhardtii, and isolated homoplasmic plastid transformants. The catalytic activity of the recombinant E.

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