scholarly journals Only the co‐transcriptional activity of β‐catenin is required for the local regulatory effects in hypertrophic chondrocytes on developmental bone modeling

2021 ◽  
Author(s):  
Lena I. Wolff ◽  
Astrid Houben ◽  
Christine Fabritius ◽  
Melinda Angus‐Hill ◽  
Konrad Basler ◽  
...  
Keyword(s):  
Transcriptional Activity ◽  
Hypertrophic Chondrocytes ◽  
Bone Modeling ◽  
Regulatory Effects

scholarly journals A Cell Atlas of Microbe-Responsive Processes in the Zebrafish Intestine

2020 ◽  
Author(s):  
Reegan J. Willms ◽  
Jennifer C. Hocking ◽  
Edan Foley
Keyword(s):  
Transcriptional Activity ◽  
Cell Types ◽  
Cellular Heterogeneity ◽  
Host Responses ◽  
Cellular Specificity ◽  
Direct Growth ◽  
A Cell ◽  
Microbe Interactions ◽  
Regulatory Effects ◽  
Host Microbe Interactions

ABSTRACTGut microbial products direct growth, differentiation and development in the animal host. Disruptions to host-microbe interactions have profound health consequences, that include onset of chronic inflammatory illnesses. However, we lack system-wide understanding of cell-specific responses to the microbiome. We profiled transcriptional activity in individual cells from the intestine, and associated tissue, of zebrafish larvae that we raised in the presence, or absence, of a microbiome. We uncovered extensive cellular heterogeneity in the conventional zebrafish intestinal epithelium, including previously undescribed cell types with known mammalian homologs. By comparing conventional to germ-free profiles, we mapped microbial impacts on transcriptional activity in each cell population. We revealed intricate degrees of cellular specificity in host responses to the microbiome, that included regulatory effects on patterning, metabolic and immune activity. For example, we showed that removal of microbes hindered transduction of vascular endothelial growth factor-dependent signals in the developing vasculature, resulting in impaired intestinal vascularization. Our work provides a high-resolution atlas of intestinal cellular composition in the developing fish gut and details the effects of the microbiome on each cell type.

scholarly journals Expression and localization of activin receptors during endochondral bone development

2001 ◽  
pp. 63-71 ◽  
Author(s):  
M Funaba ◽  
K Ogawa ◽  
M Abe
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Bone Development ◽  
Demineralized Bone Matrix ◽  
Bone Matrix ◽  
Hypertrophic Chondrocytes ◽  
Bone Modeling ◽  
Type I ◽  
Type Ii ◽  
Endochondral Bone ◽  
Activin Receptors

The expression and localization of activins (dimeric protein of inhibin beta subunit) and activin receptors in skeletal tissue were examined. RT-PCR revealed that cultured chondrocytes expressed mRNAs of inhibin/activin betaA and four activin receptors (two type I (ActRI and ActRIB) and two type II (ActRII and ActRIIB)). Immunohistochemical analyses showed that activin betaA, ActRI and ActRII were localized in proliferating chondrocytes and osteoblasts in tibiae of neonatal rats, and in implants of demineralized bone matrix, a well-established model of ectopic bone formation. The immunoreactivities of osteoblasts were decreased with aging in the tibiae and with progressing endochondral bone development in the implants. The strong expression of ActRI was also detected in hypertrophic chondrocytes both in the tibial growth plate and in the implants, whereas immunoreactive ActRII was lower in hypertrophic chondrocytes. Western blot analysis also showed that immunoreactive ActRI, migrating at 52 kDa, was detected only in the implants on days 9 and 11, the period of conversion from cartilage to bone. In view of the sharing of type II receptors between activins and bone morphogenetic proteins (BMPs), our findings suggest that activin/BMP activity involves in bone modeling, especially during active chondro- and osteogenesis and during the conversion from cartilage to bone.

scholarly journals The Localization of the Functional Glucocorticoid Receptor α in Human Bone

2000 ◽  
Vol 85 (2) ◽  
pp. 883-889 ◽  
Author(s):  
Emmanuel O. Abu ◽  
A. Horner ◽  
V. Kusec ◽  
J. T. Triffitt ◽  
J. E. Compston
Keyword(s):  
Glucocorticoid Receptor ◽  
Mononuclear Cells ◽  
Bone Cells ◽  
Fibrous Tissue ◽  
Receptor Expression ◽  
Human Bone ◽  
Hypertrophic Chondrocytes ◽  
Endochondral Bone Formation ◽  
Bone Modeling ◽  
Growth Plates

Glucocorticoids have well-documented effects on the skeleton, although their mechanism of action is still poorly understood. The actions of glucocorticoids on bone cells are mediated, in part, directly via specific receptors. The presence of these receptors has been demonstrated in both rodent and human osteoblastic cells in vitro, but their presence in human bone in vivo has not been reported. In this study, we have used specific affinity purified polyclonal antibodies to the functional glucocorticoid receptor α (GRα) to investigate its expression in both developing and adult human bone using sections of neonatal rib, calvarial, and vertebral bones, tibial growth plates from adolescents, and iliac crest biopsies from adults who were to undergo liver transplantation. In the tibial growth plates, GRα was predominantly expressed in the hypertrophic chondrocytes within the cartilage. In the primary spongiosa, the receptor was highly expressed by osteoblasts at sites of bone modeling. Within the bone marrow, receptors were also detected in mononuclear cells and in endothelial cells of blood vessels. In the neonatal rib and vertebrae, GRα was widely distributed at sites of endochondral bone formation in resting, proliferating, mature, and hypertrophic chondrocytes. They were also highly expressed in osteoblasts at sites of bone modeling. At sites of intramembranous ossification in neonatal calvarial bone and rib periosteum, GRα was widely expressed in cells within the fibrous tissue and in osteoblasts at both the bone-forming surface and at modeling sites. In the iliac crests from adults, GRα was predominantly expressed in osteocytes. The receptors were not detected in osteoclasts. Our results show for the first time the presence of the functional GRα in human bone in situ and suggest that the actions of glucocorticoids on bone may be mediated, in part, directly via the GR at different stages of life. The absence of receptor expression in osteoclasts also suggests that the effects of glucocorticoids on bone resorption may be mediated indirectly.

scholarly journals Hdac3 regulates bone modeling by suppressing osteoclast responsiveness to RANKL

2020 ◽  
Vol 295 (51) ◽  
pp. 17713-17723
Author(s):  
David H. H. Molstad ◽  
Anna M. Mattson ◽  
Dana L. Begun ◽  
Jennifer J. Westendorf ◽  
Elizabeth W. Bradley
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Trabecular Bone ◽  
Transcriptional Activity ◽  
Ex Vivo ◽  
Bone Mineralization ◽  
Osteoclast Differentiation ◽  
Bone Modeling ◽  
Osteoclast Number ◽  
Sphingosine 1 Phosphate

Hdac3 is a lysine deacetylase that removes acetyl groups from histones and additional proteins. Although Hdac3 functions within mesenchymal lineage skeletal cells are defined, little is known about Hdac3 activities in bone-resorbing osteoclasts. In this study we conditionally deleted Hdac3 within Ctsk-expressing cells and examined the effects on bone modeling and osteoclast differentiation in mice. Hdac3 deficiency reduced femur and tibia periosteal circumference and increased cortical periosteal osteoclast number. Trabecular bone was likewise reduced and was accompanied by increased osteoclast number per trabecular bone surface. We previously showed that Hdac3 deacetylates the p65 subunit of the NF-κB transcriptional complex to decrease DNA-binding and transcriptional activity. Hdac3-deficient osteoclasts demonstrate increased K310 NF-κB acetylation and NF-κB transcriptional activity. Hdac3-deficient osteoclast lineage cells were hyper-responsive to RANKL and showed elevated ex vivo osteoclast number and size and enhanced bone resorption in pit formation assays. Osteoclast-directed Hdac3 deficiency decreased cortical and trabecular bone mass parameters, suggesting that Hdac3 regulates coupling of bone resorption and bone formation. We surveyed a panel of osteoclast-derived coupling factors and found that Hdac3 suppression diminished sphingosine-1-phosphate production. Osteoclast-derived sphingosine-1-phosphate acts in paracrine to promote bone mineralization. Mineralization of WT bone marrow stromal cells cultured with conditioned medium from Hdac3-deficient osteoclasts was markedly reduced. Expression of alkaline phosphatase, type 1a1 collagen, and osteocalcin was also suppressed, but no change in Runx2 expression was observed. Our results demonstrate that Hdac3 controls bone modeling by suppressing osteoclast lineage cell responsiveness to RANKL and coupling to bone formation.

The Role of Zinc in Thyroid Hormones Metabolism

2019 ◽  
Vol 89 (1-2) ◽  
pp. 80-88 ◽  
Author(s):  
Juliana Soares Severo ◽  
Jennifer Beatriz Silva Morais ◽  
Taynáh Emannuelle Coelho de Freitas ◽  
Ana Letícia Pereira Andrade ◽  
Mayara Monte Feitosa ◽  
...  
Keyword(s):  
Thyroid Hormones ◽  
Scientific Evidence ◽  
Thyroid Stimulating Hormone ◽  
Zinc Transporters ◽  
Serum Concentrations ◽  
Metabolic Adaptations ◽  
Serum T3 ◽  
Regulatory Effects ◽  
Shed Light

Abstract. Thyroid hormones play an important role in body homeostasis by facilitating metabolism of lipids and glucose, regulating metabolic adaptations, responding to changes in energy intake, and controlling thermogenesis. Proper metabolism and action of these hormones requires the participation of various nutrients. Among them is zinc, whose interaction with thyroid hormones is complex. It is known to regulate both the synthesis and mechanism of action of these hormones. In the present review, we aim to shed light on the regulatory effects of zinc on thyroid hormones. Scientific evidence shows that zinc plays a key role in the metabolism of thyroid hormones, specifically by regulating deiodinases enzymes activity, thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH) synthesis, as well as by modulating the structures of essential transcription factors involved in the synthesis of thyroid hormones. Serum concentrations of zinc also appear to influence the levels of serum T3, T4 and TSH. In addition, studies have shown that Zinc transporters (ZnTs) are present in the hypothalamus, pituitary and thyroid, but their functions remain unknown. Therefore, it is important to further investigate the roles of zinc in regulation of thyroid hormones metabolism, and their importance in the treatment of several diseases associated with thyroid gland dysfunction.

The Anti-Atherogenic Properties of Sesamin are Mediated via Improved Macrophage Cholesterol Efflux Through PPARγ1-LXRα and MAPK Signaling

2014 ◽  
Vol 84 (1-2) ◽  
pp. 79-91 ◽  
Author(s):  
Amin F. Majdalawieh ◽  
Hyo-Sung Ro
Keyword(s):  
Cholesterol Efflux ◽  
Transcriptional Activity ◽  
Molecular Mechanisms ◽  
Foam Cell ◽  
Mapk Signaling ◽  
Luciferase Reporter ◽  
Foam Cell Formation ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Macrophage Cholesterol Efflux

Background: Foam cell formation resulting from disrupted macrophage cholesterol efflux, which is triggered by PPARγ1 and LXRα, is a hallmark of atherosclerosis. Sesamin and sesame oil exert anti-atherogenic effects in vivo. However, the exact molecular mechanisms underlying such effects are not fully understood. Aim: This study examines the potential effects of sesamin (0, 25, 50, 75, 100 μM) on PPARγ1 and LXRα expression and transcriptional activity as well as macrophage cholesterol efflux. Methods: PPARγ1 and LXRα expression and transcriptional activity are assessed by luciferase reporter assays. Macrophage cholesterol efflux is evaluated by ApoAI-specific cholesterol efflux assays. Results: The 50 μM, 75 μM, and 100 μM concentrations of sesamin up-regulated the expression of PPARγ1 (p< 0.001, p < 0.001, p < 0.001, respectively) and LXRα (p = 0.002, p < 0.001, p < 0.001, respectively) in a concentration-dependent manner. Moreover, 75 μM and 100 μM concentrations of sesamin led to 5.2-fold (p < 0.001) and 6.0-fold (p<0.001) increases in PPAR transcriptional activity and 3.9-fold (p< 0.001) and 4.2-fold (p < 0.001) increases in LXR transcriptional activity, respectively, in a concentration- and time-dependent manner via MAPK signaling. Consistently, 50 μM, 75 μM, and 100 μM concentrations of sesamin improved macrophage cholesterol efflux by 2.7-fold (p < 0.001), 4.2-fold (p < 0.001), and 4.2-fold (p < 0.001), respectively, via MAPK signaling. Conclusion: Our findings shed light on the molecular mechanism(s) underlying sesamin’s anti-atherogenic effects, which seem to be due, at least in part, to its ability to up-regulate PPARγ1 and LXRα expression and transcriptional activity, improving macrophage cholesterol efflux. We anticipate that sesamin may be used as a therapeutic agent for treating atherosclerosis.

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