scholarly journals Methylpiperidinopyrazole Attenuates Estrogen-Induced Mitochondrial Energy Production and Subsequent Osteoblast Maturation via an Estrogen Receptor Alpha-Dependent Mechanism

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2876
Author(s):  
Poh-Shiow Yeh ◽  
Jui-Tai Chen ◽  
Yih-Giun Cherng ◽  
Shun-Tai Yang ◽  
Yu-Ting Tai ◽  
...  
Keyword(s):  
Energy Production ◽  
Estrogen Receptor Alpha ◽  
Type I Collagen ◽  
Atp Synthesis ◽  
Neonatal Rat ◽  
Type I ◽  
Collagen Mrna ◽  
Adenosine Phosphate ◽  
Mitochondrial Energy Production ◽  
Osteoblast Maturation

An estrogen deficiency is the main cause of osteoporosis in postmenopausal women. In bone remodeling, estrogen receptors (ERs) can mediate estrogen-transducing signals. Methylpiperidinopyrazole (MPP) is a highly specific antagonist of ER-alpha (ERα). This study was designed to evaluate the effects of MPP on estrogen-induced energy production, subsequent osteoblast maturation, and the possible mechanisms. Exposure of primary osteoblasts isolated from neonatal rat calvarias to MPP did not affect cell morphology or survival. Estradiol can induce translocation of ERα into mitochondria from the cytoplasm. Interestingly, pretreatment of rat calvarial osteoblasts with MPP lowered estrogen-induced ERα translocation. Sequentially, estrogen-triggered expressions of mitochondrial energy production-linked cytochrome c oxidase (COX) I and COX II messenger (m)RNAs were inhibited following pretreatment with MPP. Consequently, MPP caused decreases in estrogen-triggered augmentation of the activities of mitochondrial respiratory complex enzymes and levels of cellular adenosine phosphate (ATP). During progression of osteoblast maturation, estrogen induced bone morphogenetic protein (BMP)-6 and type I collagen mRNA expressions, but MPP treatment inhibited such induction. Consequently, estrogen-induced osteoblast activation and mineralization were attenuated after exposure to MPP. Taken together, MPP suppressed estrogen-induced osteoblast maturation through decreasing chromosomal osteogenesis-related BMP-6 and type I collagen mRNA expressions and mitochondrial ATP synthesis due to inhibiting energy production-linked COX I and II mRNA expressions. MPP can appropriately be applied to evaluate estrogen-involved bioenergetics and osteoblast maturation.

Genistein Triggers Translocation of Estrogen Receptor-Alpha in Mitochondria to Induce Expressions of ATP Synthesis-Associated Genes and Improves Energy Production and Osteoblast Maturation

2021 ◽  
pp. 1-23
Author(s):  
Gong-Jhe Wu ◽  
Yih-Giun Cherng ◽  
Jui-Tai Chen ◽  
Chuen-Chau Chang ◽  
Shing-Hwa Liu ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Energy Production ◽  
Estrogen Receptor Alpha ◽  
Atp Synthesis ◽  
Gene Expressions ◽  
Linked Gene ◽  
Receptor Alpha ◽  
Protein Expressions ◽  
Osteoblast Maturation ◽  
Rat Osteoblasts

Our previous study showed that estrogen can induce mitochondrial adenosine triphosphate (ATP) synthesis-associated gene expressions and osteoblast maturation. Genistein, a phytoestrogenic isoflavone that is widely found in various foods and traditional herb products, is beneficial for osteogenesis by selectively triggering estrogen receptor alpha (ER[Formula: see text] expression. In this study, we further investigated the mechanisms of genistein-induced energy production and osteoblast activation. Exposure of rat calvarial osteoblasts and human U-2 OS cells to genistein triggered osteoblast activation without affecting cell survival. Treatment with genistein time-dependently induced ER[Formula: see text] mRNA and protein expressions in rat calvarial osteoblasts. Analyses by confocal microscopy and immunoblotting showed that genistein stimulated translocation of ER[Formula: see text] from the cytoplasm to mitochondria. Subsequently, expressions of mitochondrial cytochrome c oxidase (COX) I and II mRNAs and proteins in primary rat osteoblasts were induced after exposure to genistein. Knocking-down ER[Formula: see text] concurrently inhibited genistein-induced COX I and II mRNA expressions. In addition, mitochondrial complex enzyme activities, the mitochondrial membrane potential, and cellular ATP levels in rat calvarial osteoblasts were time-dependently augmented by genistein. Suppressing ER[Formula: see text] expression instantaneously lowered genistein-induced enhancements of mitochondrial energy production and osteoblast activation. Effects of genistein on ER[Formula: see text] translocation, COX I and II mRNA expressions, ATP synthesis, and osteoblast activation were further confirmed in human U-2 OS cells. This study showed that genistein can stimulate energy production and consequent osteoblast activation via inducing ER[Formula: see text]-mediated mitochondrial ATP synthesis-linked gene expressions.

Mechanical stretch modulates TGF-β1 and α1(I) collagen expression in fetal human intestinal smooth muscle cells

1999 ◽  
Vol 277 (5) ◽  
pp. G1074-G1080 ◽  
Author(s):  
Jorge A. Gutierrez ◽  
Hilary A. Perr
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Type I Collagen ◽  
Intestinal Smooth Muscle ◽  
Type I ◽  
Collagen Mrna ◽  
Collagen Expression ◽  
Collagen Protein ◽  
Mrna Content ◽  
Tgf Β1

Intestinal muscle undergoes stretch intermittently during peristalsis and persistently proximal to obstruction. The influence of this pervasive biomechanical force on developing smooth muscle cell function remains unknown. We adapted a novel in vitro system to study whether stretch modulates transforming growth factor-β1 (TGF-β1) and type I collagen protein and component α1 chain [α1(I) collagen] expression in fetal human intestinal smooth muscle cells. Primary confluent cells at 20-wk gestation, cultured on flexible silicone membranes, were subjected to two brief stretches or to 18 h tonic stretch. Nonstretched cultures served as controls. TGF-β1 protein was measured by ELISA and type I collagen protein was assayed by Western blot. TGF-β1 and α1(I) collagen mRNA abundance was determined by Northern blot analysis, quantitated by phosphorimaging, and normalized to 18S rRNA. Transcription was examined by nuclear run-on assay. Tonic stretch increased TGF-β1 protein 40%, type I collagen protein 100%, TGF-β1 mRNA content 2.16-fold, and α1(I) collagen mRNA 3.80-fold and enhanced transcription of TGF-β1 and α1(I) collagen by 3.1- and 4.25-fold, respectively. Brief stretch stimulated a 50% increase in TGF-β1 mRNA content but no change in α1(I) collagen. Neutralizing anti-TGF-β1 ablated stretch-mediated effects on α1(I) collagen. Therefore, stretch upregulates transcription for TGF-β1, which stimulates α1(I) collagen gene expression in smooth muscle from developing gut.

Delivery of a Hammerhead Ribozyme Specifically Downregulates Mutant Type I Collagen mRNA in a Murine Model of Osteogenesis Imperfecta

2001 ◽  
Vol 11 (5) ◽  
pp. 341-346 ◽  
Author(s):  
Ivanka Toudjarska ◽  
Michael W. Kilpatrick ◽  
Junqi Niu ◽  
Richard J. Wenstrup ◽  
Petros Tsipouras
Keyword(s):  
Osteogenesis Imperfecta ◽  
Murine Model ◽  
Type I Collagen ◽  
Hammerhead Ribozyme ◽  
Type I ◽  
Mutant Type ◽  
Collagen Mrna

Increased expression of eukaryotic initiation factor 4E during growth of neonatal rat cardiocytes in vitro

1998 ◽  
Vol 274 (6) ◽  
pp. H2133-H2142 ◽  
Author(s):  
Antoine A. Makhlouf ◽  
Paul J. McDermott
Keyword(s):  
Type I Collagen ◽  
Neonatal Rat ◽  
Initiation Factor ◽  
Translational Efficiency ◽  
Type I ◽  
Mrna Levels ◽  
Eukaryotic Initiation Factor ◽  
Translational Initiation ◽  
Hypertrophic Growth ◽  
Eukaryotic Initiation Factor 4E

Eukaryotic initiation factor 4E (eIF-4E) is rate limiting for translational initiation. The purpose of this study was to determine whether eIF-4E levels are increased during cardiocyte growth produced by increased load in the form of electrically stimulated contraction. Neonatal rat cardiocytes were cultured on a matrix of aligned type I collagen. The cardiocytes aligned in parallel to the direction of the collagen fibrils and exhibited an elongated, rod-shaped morphology. Cardiocytes were electrically stimulated to contract at 3 Hz (alternating polarity, 5-ms pulse width). Nonstimulated cardiocytes were quiescent and used as controls. Electrically stimulated contraction produced hypertrophic growth as determined by the following criteria: 1) increased protein content, 2) increased RNA content, 3) accelerated rate of protein synthesis, and 4) threefold increase in promoter activity of the atrial natriuretic factor gene. Cardiocyte growth was associated with an increase in eIF-4E mRNA levels that reached 48 ± 9% after 2 days of electrically stimulated contraction. eIF-4E protein levels were increased by more than twofold over the same time period. We conclude that an adaptive increase in eIF-4E is an important mechanism for maintaining translational efficiency during cardiocyte growth.

scholarly journals Regulation of type I collagen mRNA in lung fibroblasts by cystine availability

1998 ◽  
Vol 331 (2) ◽  
pp. 417-422 ◽  
Author(s):  
David C. RISHIKOF ◽  
Ping-Ping KUANG ◽  
Christine POLIKS ◽  
Ronald H. GOLDSTEIN
Keyword(s):  
Amino Acids ◽  
Steady State ◽  
Amino Acid ◽  
Type I Collagen ◽  
State Level ◽  
Lung Fibroblasts ◽  
Type I ◽  
Mrna Levels ◽  
Collagen Mrna ◽  
Amino Acid Availability

The steady-state level of α1(I) collagen mRNA is regulated by amino acid availability in human lung fibroblasts. Depletion of amino acids decreases α1(I) collagen mRNA levels and repletion of amino acids induces rapid re-expression of α1(I) mRNA. In these studies, we examined the requirements for individual amino acids on the regulation of α1(I) collagen mRNA. We found that re-expression of α1(I) collagen mRNA was critically dependent on cystine but not on other amino acids. However, the addition of cystine alone did not result in re-expression of α1(I) collagen mRNA. Following amino acid depletion, the addition of cystine with selective amino acids increased α1(I) collagen mRNA levels. The combination of glutamine and cystine increased α1(I) collagen mRNA levels 6.3-fold. Methionine or a branch-chain amino acid (leucine, isoleucine or valine) also acted in combination with cystine to increase α1(I) collagen mRNA expression, whereas other amino acids were not effective. The prolonged absence of cystine lowered steady-state levels of α1(I) collagen mRNA through a mechanism involving decreases in both the rate of gene transcription as assessed by nuclear run-on experiments and mRNA stability as assessed by half-life determination in the presence of actinomycin D. The effect of cystine was not mediated via alterations in the level of glutathione, the major redox buffer in cells, as determined by the addition of buthionine sulphoximine, an inhibitor of γ-glutamylcysteine synthetase. These data suggest that cystine directly affects the regulation of α1(I) collagen mRNA.

Morphological and Functional Characteristics of Three-Dimensional Engineered Bone-Ligament-Bone Constructs Following Implantation

2009 ◽  
Vol 131 (10) ◽  
Author(s):  
Jinjin Ma ◽  
Kristen Goble ◽  
Michael Smietana ◽  
Tatiana Kostrominova ◽  
Lisa Larkin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Type I Collagen ◽  
Three Dimensional ◽  
Functionally Graded ◽  
Neonatal Rat ◽  
Ligament Injury ◽  
Type I ◽  
Tangent Moduli

The incidence of ligament injury has recently been estimated at 400,000/year. The preferred treatment is reconstruction using an allograft, but outcomes are limited by donor availability, biomechanical incompatibility, and immune rejection. The creation of an engineered ligament in vitro solely from patient bone marrow stromal cells (has the potential to greatly enhance outcomes in knee reconstructions. Our laboratory has developed a scaffoldless method to engineer three-dimensional (3D) ligament and bone constructs from rat bone marrow stem cells in vitro. Coculture of these two engineered constructs results in a 3D bone-ligament-bone (BLB) construct with viable entheses, which was successfully used for medial collateral ligament (MCL) replacement in a rat model. 1 month and 2 month implantations were applied to the engineered BLBs. Implantation of 3D BLBs in a MCL replacement application demonstrated that our in vitro engineered tissues grew and remodeled quickly in vivo to an advanced phenotype and partially restored function of the knee. The explanted 3D BLB ligament region stained positively for type I collagen and elastin and was well vascularized after 1 and 2 months in vivo. Tangent moduli of the ligament portion of the 3D BLB 1 month explants increased by a factor of 2.4 over in vitro controls, to a value equivalent to those observed in 14-day-old neonatal rat MCLs. The 3D BLB 1 month explants also exhibited a functionally graded response that closely matched native MCL inhomogeneity, indicating the constructs functionally adapted in vivo.

Impact of TNF-α On Type I Collagen mRNA Expression in Cultured Muscle Cell Types

2006 ◽  
Vol 38 (Supplement) ◽  
pp. S281 ◽  
Author(s):  
Luc E. Gosselin ◽  
Kathleen McCormick ◽  
Jacqueline Williams
Keyword(s):  
Mrna Expression ◽  
Muscle Cell ◽  
Type I Collagen ◽  
Cell Types ◽  
Type I ◽  
Collagen Mrna ◽  
Tnf Α
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