Propranolol attenuates calorie restriction- and high calorie diet-induced bone marrow adiposity

( Kyunghwa Baek ),( Hyun Jung Park ),( Hyo Rin Hwan ),( Jeong Hwa Baek ) 생화학분자생물학회(구 한국생화학분자생물학회) 2014 BMB Reports Vol.47 No.10

We investigated the effects of β-adrenergic activation on bone marrow adiposity and on adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). C57BL/6 mice were subjected to a control (CON), high calorie (HIGH) or low calorie (LOW) diet for 12 weeks. In each group, mice were treated with vehicle (VEH) or propranolol. The number of adipocytes per area bone marrow was increased in LOWVEHand HIGHVEH mice compared with CONVEH mice, which was attenuated by propranolol. Isoproterenol increased lipid droplet accumulation and adipogenic marker gene expression in 3T3-L1 preadipocytes and mouse BMSCs, which were blocked by propranolol. Conditioned medium obtained from MC3T3-E1 osteoblasts suppressed adipogenic differentiation of 3T3-L1 cells, which was significantly attenuated by treatment of MC3T3-E1 cells with isoproterenol. These data suggest that β-adrenergic activation enhances bone marrow adipogenesis via direct stimulation of BMSCs adipogenesis and indirect inhibition of osteoblast anti-adipogenic potential.

The transcription factors myeloid elf-1-like factor (MEF) and distal-less homeobox 5 (Dlx5) inversely regulate the differentiation of osteoblasts and adipocytes in bone marrow

Baek, Kyunghwa,Baek, Jeong-Hwa Landes Bioscience 2013 Adipocyte Vol.2 No.1

<P>In bone marrow, the differentiation of osteoblasts and adipocytes is reciprocally regulated. This inverse regulation occurs mainly through complex signaling crosstalk between transcriptional factors such as peroxisome proliferator-activated receptor-γ (PPARγ) and runt-related transcription factor 2 (Runx2). This commentary addresses the role of myeloid elf-1 like factor (MEF) and distal-less homeobox 5 (Dlx5) in the lineage commitment of bone marrow mesenchymal stem cells into adipocytes and osteoblasts, respectively. MEF suppresses osteoblastogenesis by preventing Runx2 from binding to the promoters of target genes and enhancing adipogenesis via transactivation of PPARγ expression. Conversely, Dlx5 enhances osteoblastogenesis through upregulation of the expression of Runx2 and osteoblast marker genes while suppressing adipogenesis through the downregulation of PPARγ expression by sequestering the cAMP response element binding protein and CCAAT/enhancer-binding protein α. Studies designed to examine the effects of physiological and pathologic signals on the expression of MEF and Dlx5 will provide further insight to the function of these transcription factors in vivo.</P>

Hypoxia Inducible Factor-1α Directly Induces the Expression of Receptor Activator of Nuclear Factor-κB Ligand in Chondrocytes

Kyunghwa Baek,Hyun-Jung Park,Jeong-Hwa Baek 대한구강생물학회 2016 International Journal of Oral Biology Vol.41 No.1

Receptor activator of nuclear factor-κB ligand (RANKL) is an osteoblast/stromal cell-derived essential factor for osteoclastogenesis. During endochondral bone formation, hypertrophic chondrocytes calcify cartilage matrix that is subsequently resorbed by osteoclasts in order to be replaced by new bone. Hypoxia-induced upregulation of RANKL expression has been previously demonstrated in an in vitro system using osteoblasts; however, the involved mechanism remains unclear in chondrocytes. In the present study, we investigated whether hypoxia regulates RANKL expression in ATDC5 cells, a murine chondrogenic cell line, and hypoxiainducible factor-1α (HIF-1α) mediates hypoxia-induced RANKL expression by transactivating the RANKL promoter. The expression levels of RANKL mRNA and protein, as well as HIF-1α protein, were significantly increased in ATDC5 cells under hypoxic condition. Constitutively active HIF-1α alone significantly increased the levels of RANKL expression under normoxic conditions, whereas dominant negative HIF-1α reduced hypoxia-induced RANKL expression. HIF-1α increased RANKL promoter reporter activity in a HIF-1α binding element-dependent manner in ATDC5 cells. Hypoxia-induced RANKL levels were much higher in differentiated ATDC5 cells, as compared to proliferating ATDC5 cells. These results suggested that under hypoxic conditions, HIF-1α mediates induction of RANKL expression in chondrocytes; in addition, hypoxia plays a role in osteoclastogenesis during endochondral bone formation, at least in part, through the induction of RANKL expression in hypertrophic chondrocytes.

Hypoxia Inducible Factor-1α Directly Induces the Expression of Receptor Activator of Nuclear Factor-κB Ligand in MLO-Y4 Osteocytes

Kyunghwa Baek,Hyun-Jung Park,Jeong-Hwa Baek 대한구강생물학회 2015 International Journal of Oral Biology Vol.40 No.1

Osteocytes may function as mechanotransducers byregulating local osteoclastogenesis. Reduced availability ofoxygen, i.e. hypoxia, could occur during disuse, bonedevelopment, and fracture. Receptor activator of nuclearfactor-κB ligand (RANKL) is an osteoblast/stromal cellderived essential factor for osteoclastogenesis. The hypoxiainduced osteoclastogenesis via increased RANKL expressionin osteoblasts was demonstrated. Hypoxic regulation of geneexpression generally involves activation of thehypoxia-inducible factor (HIF) transcription pathway. In thepresent study, we investigated whether hypoxia regulatesRANKL expression in murine osteocytes and HIF-1αmediates hypoxia-induced RANKL expression bytransactivating RANKL promoter, to elucidate the role ofosteocyte in osteoclastogenesis in the context of hypoxiccondition. The expression levels of RANKL mRNA andprotein, as well as hypoxia inducible factor-1α (HIF-1α)protein, were significantly increased in hypoxic condition inMLO-Y4s. Constitutively active HIF-1α alone significantlyincreased the levels of RANKL expression in MLO-Y4sunder normoxic conditions, whereas dominant negativeHIF-1α blocked hypoxia-induced RANKL expression. Tofurther explore to find if HIF-1α directly regulates RANKLtranscription, a luciferase reporter assay was conducted. Hypoxia significantly increased RANKL promoter activity,whereas mutations of putative HIF-1α binding elements inRANKL promoter prevented this hypoxia-induced RANKLpromoter activity in MLO-Y4s. These results suggest thatHIF-1α mediates hypoxia-induced up-regulation of RANKLexpression, and that in osteocytes of mechanically unloadedbone, hypoxia enhances osteoclastogenesis, at least in part, viaan increased RANKL expression in osteocytes.

TNFα Increases the Expression of β2 Adrenergic Receptors in Osteoblasts

Kyunghwa Baek,Hye-Lim Lee,Hyo Rin Hwang,Hyun-Jung Park,Arang Kwon,Abdul S. Qadir,Jeong-Hwa Baek KOREAN ACADAMY OF ORAL BIOLOGY 2011 International Journal of Oral Biology Vol.36 No.4

Tumor necrosis factor alpha (TNFα) is a multifunctional cytokine that is elevated in inflammatory diseases such as atherosclerosis, diabetes and rheumatoid arthritis. Recent evidence has suggested that β2 adrenergic receptor (β2AR) activation in osteoblasts suppresses osteogenic activity. In the present study, we explored whether TNFα modulates βAR expression in osteoblastic cells and whether this regulation is associated with the inhibition of osteoblast differentiation by TNFα. In the experiments, we used C2C12 cells, MC3T3-E1 cells and primary cultured mouse bone marrow stromal cells. Among the three subtypes of βAR, β2 and β3AR were found in our analysis to be upregulated by TNFα. Moreover, isoproterenol-induced cAMP production was observed to be significantly enhanced in TNFα-primed C2C12 cells, indicating that TNFα enhances β2AR signaling in osteoblasts. TNFα was further found in C2C12 cells to suppress bone morphogenetic protein 2-induced alkaline phosphatase (ALP) activity and the expression of osteogenic marker genes including Runx2, ALP and osteocalcin. Propranolol, a β2AR antagonist, attenuated this TNFα suppression of osteogenic differentiation. TNFα increased the expression of receptor activator of NF-κB ligand (RANKL), an essential osteoclastogenic factor, in C2C12 cells which was again blocked by propranolol. In summary, our data show that TNFα increases β2AR expression in osteoblasts and that a blockade of β2AR attenuates the suppression of osteogenic differentiation and stimulation of RANKL expression by TNFα. These findings imply that a crosstalk between TNFα and β2AR signaling pathways might occur in osteoblasts to modulate their function.

Tumor Necrosis Factor α up-regulates the Expression of beta2 Adrenergic Receptor via NF-κB-dependent Pathway in Osteoblasts

Kyunghwa Baek,Jiho Kang,Hyo Rin Hwang,Jeong-Hwa Baek The Korean Academy of Oral Biology 2013 International Journal of Oral Biology Vol.38 No.3

Tumor necrosis factor alpha (TNFα) is a multifunctional inflammatory cytokine that regulates various cellular and biological processes. Increased levels of TNFα have been implicated in a number of human diseases including diabetes and arthritis. Sympathetic nervous system stimulation via the beta2-adrenergic receptor (β2AR) in osteoblasts suppresses osteogenic activity. We previously reported that TNFα upregulates β2AR expression in murine osteoblastic cells and that this modulation is associated with TNFα inhibition of osteoblast differentiation. In our present study, we explored whether TNFα induces β2AR expression in human osteoblasts and then identified the downstream signaling pathway. Our results indicated that β2AR expression was increased in Saos-2 and C2C12 cells by TNFα treatment, and that this increase was blocked by the inhibition of NF-κB activation. Chromatin immunoprecipitation and luciferase reporter assay results indicated that NF-κB directly binds to its cognate elements on the β2AR promoter and thereby stimulates β2AR expression. These findings suggest that the activation of TNFα signaling in osteoblastic cells leads to an upregulation of β2AR and also that TNFα induces β2AR expression in an NF-κB-dependent manner.

Rheinheimera aestuari sp. nov., a marine bacterium isolated from coastal sediment.

Baek, Kyunghwa,Jeon, Che Ok Society for General Microbiology 2015 International journal of systematic and evolutiona Vol.65 No.8

<P>A Gram-stain-negative, strictly aerobic, non-pigmented, motile bacterium with a single polar flagellum, designated H29T, was isolated from coastal sediment of Jeju Island, South Korea. Cells were non-spore-forming rods showing catalase- and oxidase-positive reactions. Growth of strain H29T was observed at 10-40?C (optimum, 20-25?C) and pH?6.0-9.0 (optimum, pH?7.0-8.0), and in the presence of 1-4?% (w/v) NaCl (optimum, 2-3?%). Strain H29T contained C16?:?0, iso-C15?:?0 3-OH and summed feature 3 (comprising C16?:?1ω7c/C16?:?1ω6c) as the major fatty acids and ubiquinone-8 (Q-8) as the sole isoprenoid quinone. Phosphatidylethanolamine and phosphatidylglycerol were identified as the major polar lipids. The G+C content of the genomic DNA was 46.5?mol%. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain H29T formed a phyletic lineage with Rheinheimera hassiensis E48T within the genus Rheinheimera of the family Chromatiaceae. Strain H29T was most closely related to Rheinheimera pacifica KMM 1406T, Rheinheimera muenzenbergensis E49T, Rheinheimera hassiensis E48T and Rheinheimera baltica OSBAC1T with 97.8?%, 97.6?%, 97.4?% and 97.2?% 16S rRNA gene sequence similarities, respectively. However, DNA-DNA hybridization values of strain H29T with type strains of these species were lower than 70?%. On the basis of the phenotypic, chemotaxonomic and molecular properties, strain H29T represents a novel species of the genus Rheinheimera, for which the name Rheinheimeraaestuarii sp. nov. is proposed. The type strain is H29T (?=?KACC 18251T?=?JCM 30404T).</P>

Mucilaginibacter vulcanisilvae sp. nov., isolated from a volcanic forest

Baek, Kyunghwa,Ok Jeon, Che Microbiology Society 2015 International journal of systematic and evolutiona Vol.65 No.7

An overview of the endocrine functions of osteocalcin

Kyunghwa Baek 대한구강생물학회 2019 International Journal of Oral Biology Vol.44 No.4

Osteocalcin is the most abundant non-collagenous protein produced in bone. It has traditionally been regarded as a marker of bone turnover and is thought to act in the bone matrix to regulate mineralization. However, emerging knowledge regarding osteocalcin has expanded to include functions in energy metabolism, fertilization, and regulation of cognition. Fully carboxylated osteocalcin binds to hydroxyapatite, thereby modulating bone turnover, whereas undercarboxylated osteocalcin in the circulation binds to osteocalcin-sensing receptors and acts as a hormone that affects multiple physiological aspects. In this review, we summarize the current knowledge regarding the hormonal actions of osteocalcin in various organs and potential cellular downstream signaling pathway that may be involved.

Blocking β ₁ /β ₂ -Adrenergic Signaling Reduces Dietary Fat Absorption by Suppressing Expression of Pancreatic Lipase in High Fat-Fed Mice

Baek, Kyunghwa,Park, Danbi,Hwang, Hyo Rin,Kim, Seong-Gon,Lee, Heesu,Baek, Jeong-Hwa MDPI 2018 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.19 No.3

<P>We investigated whether β-adrenergic antagonists attenuates dietary fat absorption through the regulation of pancreatic lipase (PNLIP) expression in pancreatic acinar cells in the context of high fat diet feeding. Male six-week-old C57BL/6 mice were assigned into an ad libitum fed control diet (CON) and a high fat diet (HIGH). Within each diet group, subgroups of mice were treated with vehicle (VEH) or propranolol, a β-adrenergic antagonist (BB). Over 12 weeks, body weight gain observed in HIGHVEH was mitigated in HIGHBB (+103% vs. +72%). Increase in fecal fat amount observed in HIGHVEH was further increased in HIGHBB. Increase in PNLIP expressions observed in HIGHVEH pancreatic tissues was abolished in HIGHBB. PNLIP expression in mouse primary pancreatic acinar cells and 266-6 cell lines increased with isoproterenol treatment, which was blocked by propranolol. Isoproterenol increased PNLIP expression in a cAMP/protein kinase A/ cyclic AMP response element binding protein (CREB)-dependent manner. CREB directly bound to the CRE on the mouse PNLIP promoter and transactivated PNLIP expression. These results suggest that sympathetic activation increases dietary fat absorption through the upregulation of PNLIP expression and that a β-adrenergic antagonist attenuates obesity development partly through the downregulation of PNLIP expression and inhibition of dietary fat absorption in the context of high fat diet feeding.</P>