6 results on '"Carlsten, Hans"'
Search Results
2. The effect of estrogen on bone requires ERα in nonhematopoietic cells but is enhanced by ERα in hematopoietic cells
- Author
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Henning, Petra, primary, Ohlsson, Claes, additional, Engdahl, Cecilia, additional, Farman, Helen, additional, Windahl, Sara H., additional, Carlsten, Hans, additional, and Lagerquist, Marie K., additional
- Published
- 2014
- Full Text
- View/download PDF
3. Exosomal secretion of death bullets: a new way of apoptotic escape?
- Author
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Trokovic, Nina, primary, Pöllänen, Raimo, additional, Porola, Pauliina, additional, Stegaev, Vasily, additional, Hetzel, Udo, additional, Tivesten, Åsa, additional, Engdahl, Cecilia, additional, Carlsten, Hans, additional, Forsblad-d'Elia, Helena, additional, Fagman, Johan Bourghardt, additional, Lagerquist, Marie, additional, and Konttinen, Yrjö T., additional
- Published
- 2012
- Full Text
- View/download PDF
4. SERMs have substance-specific effects on bone, and these effects are mediated via ERαAF-1 in female mice.
- Author
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Börjesson AE, Farman HH, Movérare-Skrtic S, Engdahl C, Antal MC, Koskela A, Tuukkanen J, Carlsten H, Krust A, Chambon P, Sjögren K, Lagerquist MK, Windahl SH, and Ohlsson C
- Subjects
- Animals, Bone Density drug effects, Dose-Response Relationship, Drug, Female, Mice, Mice, Inbred C57BL, Organ Size drug effects, Organ Size physiology, Ovariectomy, Signal Transduction drug effects, Signal Transduction physiology, Bone Density physiology, Estrogen Receptor Modulators administration & dosage, Estrogen Receptor alpha metabolism, Lumbar Vertebrae drug effects, Lumbar Vertebrae physiology
- Abstract
The bone-sparing effect of estrogens is mediated primarily via estrogen receptor (ER)α, which stimulates gene transcription through activation function (AF)-1 and AF-2. The role of ERαAF-1 for the estradiol (E2) effects is tissue specific. The selective ER modulators (SERMs) raloxifene (Ral), lasofoxifene (Las), and bazedoxifene (Bza) can be used to treat postmenopausal osteoporosis. They all reduce the risk for vertebral fractures, whereas Las and partly Bza, but not Ral, reduce the risk for nonvertebral fractures. Here, we have compared the tissue specificity of Ral, Las, and Bza and evaluated the role of ERαAF-1 for the effects of these SERMs, with an emphasis on bone parameters. We treated ovariectomized (OVX) wild-type (WT) mice and OVX mice lacking ERαAF-1 (ERαAF-1(0)) with E2, Ral, Las, or Bza. All three SERMs increased trabecular bone mass in the axial skeleton. In the appendicular skeleton, only Las increased the trabecular bone volume/tissue volume and trabecular number, whereas both Ral and Las increased the cortical bone thickness and strength. However, Ral also increased cortical porosity. The three SERMs had only a minor effect on uterine weight. Notably, all evaluated effects of these SERMs were absent in ovx ERαAF-1(0) mice. In conclusion, all SERMs had similar effects on axial bone mass. However, the SERMs had slightly different effects on the appendicular skeleton since only Las increased the trabecular bone mass and only Ral increased the cortical porosity. Importantly, all SERM effects require a functional ERαAF-1 in female mice. These results could lead to development of more specific treatments for osteoporosis., (Copyright © 2016 the American Physiological Society.)
- Published
- 2016
- Full Text
- View/download PDF
5. The effect of estrogen on bone requires ERα in nonhematopoietic cells but is enhanced by ERα in hematopoietic cells.
- Author
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Henning P, Ohlsson C, Engdahl C, Farman H, Windahl SH, Carlsten H, and Lagerquist MK
- Subjects
- Animals, Bone Density drug effects, Bone Marrow Transplantation, Chimera, Female, Mice, Mice, Knockout, Ovariectomy, Bone and Bones drug effects, Estradiol pharmacology, Estrogen Receptor alpha physiology, Estrogens pharmacology, Osteoblasts drug effects, Osteoclasts drug effects
- Abstract
The effects of estrogen on bone are mediated mainly via estrogen receptor (ER)α. ERα in osteoclasts (hematopoietic origin) is involved in the trabecular bone-sparing effects of estrogen, but conflicting data are reported on the role of ERα in osteoblast lineage cells (nonhematopoietic origin) for bone metabolism. Because Cre-mediated cell-specific gene inactivation used in previous studies might be confounded by nonspecific and/or incomplete cell-specific ERα deletion, we herein used an alternative approach to determine the relative importance of ERα in hematopoietic (HC) and nonhematopoietic cells (NHC) for bone mass. Chimeric mice with selective inactivation of ERα in HC or NHC were created by bone marrow transplantations of wild-type (WT) and ERα-knockout (ERα(-/-)) mice. Estradiol treatment increased both trabecular and cortical bone mass in ovariectomized WT/WT (defined as recipient/donor) and WT/ERα(-/-) mice but not in ERα(-/-)/WT or ERα(-/-)/ERα(-/-) mice. However, estradiol effects on both bone compartments were reduced (∼50%) in WT/ERα(-/-) mice compared with WT/WT mice. The effects of estradiol on fat mass and B lymphopoiesis required ERα specifically in NHC and HC, respectively. In conclusion, ERα in NHC is required for the effects of estrogen on both trabecular and cortical bone, but these effects are enhanced by ERα in HC., (Copyright © 2014 the American Physiological Society.)
- Published
- 2014
- Full Text
- View/download PDF
6. Exosomal secretion of death bullets: a new way of apoptotic escape?
- Author
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Trokovic N, Pöllänen R, Porola P, Stegaev V, Hetzel U, Tivesten Å, Engdahl C, Carlsten H, Forsblad-d'Elia H, Fagman JB, Lagerquist M, and Konttinen YT
- Subjects
- Amylases metabolism, Androgens physiology, Animals, Caspase 3 metabolism, Caspase 8 metabolism, Cells, Cultured, Dihydrotestosterone pharmacology, Epithelial Cells drug effects, Female, Fluorescent Antibody Technique, Indirect, Humans, Immunohistochemistry, In Situ Nick-End Labeling, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Microscopy, Electron, Transmission, Ovariectomy, Receptors, Androgen genetics, Receptors, Androgen physiology, Salivary Proteins and Peptides metabolism, Seminal Plasma Proteins metabolism, Submandibular Gland cytology, Transaminases metabolism, Apoptosis physiology, Cell Death physiology, Exosomes physiology
- Abstract
Ovariectomy/estrogen deficiency causes selective apoptosis of the serous epithelial cells of the submandibular glands (SMG) in female mice. Because such apoptosis does not occur in healthy, estrogen-deficient male mice, it was hypothesized that dihydrotestosterone (DHT) protects epithelial SMG cells against apoptosis. The antiapoptotic effect of DHT on human epithelial HSG cells exposed to tumor necrosis factor-α and cycloheximide was studied. Correspondingly, the proapoptotic effect of androgen deficiency was studied in orchiectomized (ORX) androgen-knockout (ARKO) and wild-type (WT) mice. The health state of the SMG cells was studied with Alcian blue-periodic acid Schiff (AB-PAS) and amylase staining and transmission electron microscopy (TEM). The eventual protective antiapoptotic effect of dehydroepiandrosterone (DHEA) treatment was tested in this model. Apoptosis was assessed using immunohistochemisty of cleaved effector caspase-3 and its activator caspase-8 and the TUNEL assay. To test for the bioavailability, intracrine metabolism and sex steroid effects of DHEA, cystein-rich secretory protein-3 (CRISP-3), and leucine-isoleucine-valine transport system 1 (LIV-1) were used as androgen- and estrogen-regulated biomarkers, respectively. DHT protected HSG cells against induced apoptosis. In mice, androgen deficiency resulted in extensive activation of apoptotic caspase-8/3 cascade in serous epithelial cells. However, in salivary glands, active caspases were not translocated to nuclei but secreted to salivary ducts in exosome-like particles, which are associated with weak AB-PAS and amylase staining of the androgen-deprived cells and reduced number of intracellular secretory granules. DHEA treatment suppressed induction of proapoptotic caspases and almost normalized mucins and amylase and ultramophology of the serous epithelial cells in WT ORX but not ARKO ORX mice. According to the CRISP-3 and LIV-1 markers, DHEA probably exerted its effects via intracrine conversion to DHT.
- Published
- 2012
- Full Text
- View/download PDF
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