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Article ; Online: Osteocalcin promotes bone mineralization but is not a hormone.

Manolagas, Stavros C

2020 Volume 16, Issue 6, Page(s) e1008714

MeSH term(s)	Alkaline Phosphatase ; Animals ; Calcification, Physiologic ; Mice ; Osteocalcin
Chemical Substances	Osteocalcin (104982-03-8) ; Alkaline Phosphatase (EC 3.1.3.1)
Language	English
Publishing date	2020-06-02
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2186725-2
ISSN	1553-7404 ; 1553-7390
ISSN (online)	1553-7404
ISSN	1553-7390
DOI	10.1371/journal.pgen.1008714
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The Quest for Osteoporosis Mechanisms and Rational Therapies: How Far We've Come, How Much Further We Need to Go.

Manolagas, Stavros C

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

2018 Volume 33, Issue 3, Page(s) 371–385

Abstract: During the last 40 years, understanding of bone biology and the pathogenesis of osteoporosis, the most common and impactful bone disease of old age, has improved dramatically thanks to basic and clinical research advances, genetic insights from humans ... ...

Abstract	During the last 40 years, understanding of bone biology and the pathogenesis of osteoporosis, the most common and impactful bone disease of old age, has improved dramatically thanks to basic and clinical research advances, genetic insights from humans and rodents, and newer imaging technologies. Culprits of osteoporosis are no longer a matter of speculation based on in vitro observations. Instead, they can be identified and dissected at the cellular and molecular level using genetic approaches; and their effect on distinct bone envelopes and anatomic regions can be functionally assessed in vivo. The landscape of pharmacotherapies for osteoporosis has also changed profoundly with the emergence of several potent antiresorptive drugs as well as anabolic agents, displacing estrogen replacement as the treatment of choice. In spite of these major positive developments, the optimal duration of the available therapies and their long-term safety remain matters of conjecture and some concern. Moreover, antiresorptive therapies are used indiscriminately for patients of all ages on the assumption that suppressing remodeling is always beneficial for bone, but rebound remodeling upon their discontinuation suggests otherwise. In this invited perspective, I highlight the latest state of knowledge of bone-intrinsic and extrinsic mechanisms responsible for the development of osteoporosis in both sexes; differences between the mechanisms responsible for the effects of aging and estrogen deficiency; and the role of old osteocytes in the development of cortical porosity. In addition, I highlight advances toward the goal of developing drugs for several degenerative diseases of old age at once, including osteoporosis, by targeting shared mechanisms of aging. © 2018 American Society for Bone and Mineral Research.
MeSH term(s)	Animals ; Biological Evolution ; Bone Density ; Bone and Bones/pathology ; Bone and Bones/physiopathology ; Cellular Senescence ; Estrogens/deficiency ; Humans ; Mice ; Osteoporosis/immunology ; Osteoporosis/pathology ; Osteoporosis/physiopathology ; Osteoporosis/therapy ; Oxidative Stress ; Reactive Oxygen Species/metabolism ; Reproducibility of Results
Chemical Substances	Estrogens ; Reactive Oxygen Species
Language	English
Publishing date	2018-02-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	632783-7
ISSN	1523-4681 ; 0884-0431
ISSN (online)	1523-4681
ISSN	0884-0431
DOI	10.1002/jbmr.3400
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Zs.A 2142: Show issues

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Article ; Online: Retraction notice to "Deletion of the scavenger receptor Scarb1 in myeloid cells does not affect bone mass" [Bone 170(2023) 116702].

Palmieri, Michela / Joseph, Teenamol E / O'Brien, Charles A / Gomez-Acevedo, Horacio / Kim, Ha-Neui / Manolagas, Stavros C / Ambrogini, Elena

Bone

2023 Volume 176, Page(s) 116885

Language	English
Publishing date	2023-08-24
Publishing country	United States
Document type	Journal Article ; Retraction of Publication
ZDB-ID	632515-4
ISSN	1873-2763 ; 8756-3282
ISSN (online)	1873-2763
ISSN	8756-3282
DOI	10.1016/j.bone.2023.116885
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Zs.A 1571: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 332: Show issues

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Article ; Online: Retraction: Deletion of the scavenger receptor Scarb1 in osteoblast progenitors does not affect bone mass.

Palmieri, Michela / Joseph, Teenamol E / O'Brien, Charles A / Gomez-Acevedo, Horacio / Manolagas, Stavros C / Ambrogini, Elena

PloS one

2023 Volume 18, Issue 8, Page(s) e0290458

Language	English
Publishing date	2023-08-16
Publishing country	United States
Document type	Retraction of Publication
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0290458
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Article ; Online: Wnt signaling and osteoporosis.

Manolagas, Stavros C

Maturitas

2014 Volume 78, Issue 3, Page(s) 233–237

Abstract: Major advances in understanding basic bone biology and the cellular and molecular mechanisms responsible for the development of osteoporosis, over the last 20 years, have dramatically altered the management of this disease. The purpose of this mini- ... ...

Abstract	Major advances in understanding basic bone biology and the cellular and molecular mechanisms responsible for the development of osteoporosis, over the last 20 years, have dramatically altered the management of this disease. The purpose of this mini-review is to highlight the seminal role of Wnt signaling in bone homeostasis and disease and the emergence of novel osteoporosis therapies by targeting Wnt signaling with drugs.
MeSH term(s)	Bone and Bones/metabolism ; Humans ; Osteoporosis/drug therapy ; Osteoporosis/metabolism ; Signal Transduction ; Wnt Proteins/metabolism
Chemical Substances	Wnt Proteins
Language	English
Publishing date	2014-04-24
Publishing country	Ireland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	80460-5
ISSN	1873-4111 ; 0378-5122
ISSN (online)	1873-4111
ISSN	0378-5122
DOI	10.1016/j.maturitas.2014.04.013
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Zs.A 1432: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 575: Show issues

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Article ; Online: RETRACTED: Deletion of the scavenger receptor Scarb1 in myeloid cells does not affect bone mass

Palmieri, Michela / Joseph, Teenamol E / O'Brien, Charles A / Gomez-Acevedo, Horacio / Kim, Ha-Neui / Manolagas, Stavros C / Ambrogini, Elena

publication RETRACTED

Bone

2023 Volume 170, Page(s) 116702

Abstract: The scavenger receptor class B member 1 (SR-B1 or Scarb1) is a glycosylated cell surface receptor for high density lipoproteins (HDL), oxidized low density lipoproteins (OxLDL), and phosphocholine-containing oxidized phospholipids (PC-OxPLs). Scarb1 is ... ...

Abstract	The scavenger receptor class B member 1 (SR-B1 or Scarb1) is a glycosylated cell surface receptor for high density lipoproteins (HDL), oxidized low density lipoproteins (OxLDL), and phosphocholine-containing oxidized phospholipids (PC-OxPLs). Scarb1 is expressed in macrophages and has been shown to have both pro- and anti-atherogenic properties. It has been reported that global deletion of Scarb1 in mice leads to either high or low bone mass and that PC-OxPLs decrease osteoblastogenesis and increase osteoclastogenesis. PC-OxPLs decrease bone mass in 6-month-old mice and are critical pathogenetic factors in the bone loss caused by high fat diet or aging. We have investigated here whether Scarb1 expression in myeloid cells affects bone mass and whether PC-OxPLs exert their anti-osteogenic effects via activation of Scarb1 in macrophages. To this end, we generated mice with deletion of Scarb1 in LysM-Cre expressing cells and found that lack of Scarb1 did not affect bone mass in vivo. These results indicate that Scarb1 expression in cells of the myeloid/osteoclast lineage does not contribute to bone homeostasis. Based on this evidence, and earlier studies of ours showing that Scarb1 expression in osteoblasts does not affect bone mass, we conclude that Scarb1 is not an important mediator of the adverse effects on PC-OxPLs in osteoclasts or osteoblasts in 6-month-old mice.
MeSH term(s)	Animals ; Mice ; Scavenger Receptors, Class B/genetics ; Scavenger Receptors, Class B/metabolism ; Bone and Bones/metabolism ; Bone Density ; Osteoclasts/metabolism ; Osteogenesis
Chemical Substances	Scavenger Receptors, Class B ; Scarb1 protein, mouse
Language	English
Publishing date	2023-02-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Retracted Publication
ZDB-ID	632515-4
ISSN	1873-2763 ; 8756-3282
ISSN (online)	1873-2763
ISSN	8756-3282
DOI	10.1016/j.bone.2023.116702
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Zs.A 1571: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 332: Show issues

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Article ; Online: Steroids and osteoporosis: the quest for mechanisms.

Manolagas, Stavros C

The Journal of clinical investigation

2013 Volume 123, Issue 5, Page(s) 1919–1921

Abstract: Advances made during the last 35 years have improved our understanding of the mechanisms of steroid hormone action on bone and how physiologic, pathologic, or iatrogenic changes in hormone levels can lead to increased fracture risk. Estrogens, androgens, ...

Abstract	Advances made during the last 35 years have improved our understanding of the mechanisms of steroid hormone action on bone and how physiologic, pathologic, or iatrogenic changes in hormone levels can lead to increased fracture risk. Estrogens, androgens, and glucocorticoids alter the cellular composition of bone by regulating the supply and lifespan of osteoclasts and osteoblasts. Additionally, they influence the survival of osteocytes, long-lived cells that are entombed within the mineralized matrix and mediate the homeostatic adaptation of bone to mechanical forces. Altered redox balance is a proximal underlying mechanism of some of these effects, and sex steroid deficiency or glucocorticoid excess contributes to the aging of the skeleton.
MeSH term(s)	Animals ; Bone and Bones/metabolism ; Estrogens/metabolism ; Fracture Healing ; Glucocorticoids/metabolism ; Homeostasis ; Humans ; Osteoblasts/cytology ; Osteoclasts/cytology ; Osteocytes/physiology ; Osteoporosis/physiopathology ; Oxidation-Reduction ; RANK Ligand ; Steroids/metabolism ; Stress, Mechanical
Chemical Substances	Estrogens ; Glucocorticoids ; RANK Ligand ; Steroids
Language	English
Publishing date	2013-05-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI68062
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Ua VI Zs.184: Show issues

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Book: Metabolic bone and mineral disorders

Manolagas, Stavros C.

(Contemporary issues in endocrinology and metabolism ; 5)

1988

Author's details	ed. by Stavros C. Manolagas
Series title	Contemporary issues in endocrinology and metabolism ; 5
Collection
Keywords	Bone and Bones / metabolism ; Bone Diseases, Metabolic ; Minerals / metabolism
Size	XI, 254 S. : Ill., graph. Darst.
Publisher	Churchill Livingstone
Publishing place	New York u.a.
Publishing country	United States
Document type	Book
HBZ-ID	HT003566553
ISBN	0-443-08586-2 ; 978-0-443-08586-4
Database	Catalogue ZB MED Medicine, Health

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Shelf mark	Loan status	Location
1990 A 4488	order for loan	Magazin

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Article ; Online: Deletion of the scavenger receptor Scarb1 in osteoblast progenitors does not affect bone mass.

Palmieri, Michela / Joseph, Teenamol E / O'Brien, Charles A / Gomez-Acevedo, Horacio / Manolagas, Stavros C / Ambrogini, Elena

publication RETRACTED

PloS one

2022 Volume 17, Issue 3, Page(s) e0265893

Abstract: The scavenger receptor class B member 1 (SR-B1 or Scarb1) is a cell surface receptor for high density lipoproteins. It also binds oxidized low density lipoproteins and phosphocholine-containing oxidized phospholipids (PC-OxPL), which adversely affect ... ...

Abstract	The scavenger receptor class B member 1 (SR-B1 or Scarb1) is a cell surface receptor for high density lipoproteins. It also binds oxidized low density lipoproteins and phosphocholine-containing oxidized phospholipids (PC-OxPL), which adversely affect bone homeostasis. Overexpression of a single chain form of the antigen-binding domain of E06 IgM-a natural antibody that recognizes PC-OxPL-increases trabecular and cortical bone mass in female and male mice by stimulating bone formation. We have previously reported that Scarb1 is the most abundant scavenger receptor for PC-OxPL in calvaria-derived osteoblastic cells. Additionally, bone marrow- and calvaria-derived osteoblasts from Scarb1 knockout mice (Scarb1 KO) are protected from the pro-apoptotic and anti-differentiating effects of OxPL. Previous skeletal analysis of Scarb1 KO mice has produced contradictory results, with some studies reporting elevated bone mass but another study reporting low bone mass. To clarify the role of Scarb1 in osteoblasts, we deleted Scarb1 specifically in cells of the osteoblast lineage using Osx1-Cre transgenic mice. We observed no difference in bone mineral density measured by DXA in either female or male Osx1-Cre;Scarb1fl/fl mice compared to wild type (WT), Osx1-Cre, or Scarb1fl/fl littermate controls. Additionally, microCT analysis of 6-month-old females and 7-month-old males did not detect any difference in trabecular or cortical bone mass between genotypes. These results indicate that expression of Scarb1 in cells of the osteoblast lineage does not play an important role in bone homeostasis and, therefore, it is not essential for the effects of PC-OxPL on these cells.
MeSH term(s)	Animals ; Bone Density ; Bone and Bones/diagnostic imaging ; Female ; Male ; Mice ; Mice, Knockout ; Osteoblasts/metabolism ; Osteogenesis ; Receptors, Scavenger/metabolism ; Scavenger Receptors, Class B/genetics ; Scavenger Receptors, Class B/metabolism
Chemical Substances	Receptors, Scavenger ; Scarb1 protein, mouse ; Scavenger Receptors, Class B
Language	English
Publishing date	2022-03-29
Publishing country	United States
Document type	Journal Article ; Retracted Publication
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0265893
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis.

Manolagas, Stavros C

Endocrine reviews

2010 Volume 31, Issue 3, Page(s) 266–300

Abstract: Estrogen deficiency has been considered the seminal mechanism of osteoporosis in both women and men, but epidemiological evidence in humans and recent mechanistic studies in rodents indicate that aging and the associated increase in reactive oxygen ... ...

Abstract	Estrogen deficiency has been considered the seminal mechanism of osteoporosis in both women and men, but epidemiological evidence in humans and recent mechanistic studies in rodents indicate that aging and the associated increase in reactive oxygen species (ROS) are the proximal culprits. ROS greatly influence the generation and survival of osteoclasts, osteoblasts, and osteocytes. Moreover, oxidative defense by the FoxO transcription factors is indispensable for skeletal homeostasis at any age. Loss of estrogens or androgens decreases defense against oxidative stress in bone, and this accounts for the increased bone resorption associated with the acute loss of these hormones. ROS-activated FoxOs in early mesenchymal progenitors also divert ss-catenin away from Wnt signaling, leading to decreased osteoblastogenesis. This latter mechanism may be implicated in the pathogenesis of type 1 and 2 diabetes and ROS-mediated adverse effects of diabetes on bone formation. Attenuation of Wnt signaling by the activation of peroxisome proliferator-activated receptor gamma by ligands generated from lipid oxidation also contributes to the age-dependent decrease in bone formation, suggesting a mechanistic explanation for the link between atherosclerosis and osteoporosis. Additionally, increased glucocorticoid production and sensitivity with advancing age decrease skeletal hydration and thereby increase skeletal fragility by attenuating the volume of the bone vasculature and interstitial fluid. This emerging evidence provides a paradigm shift from the "estrogen-centric" account of the pathogenesis of involutional osteoporosis to one in which age-related mechanisms intrinsic to bone and oxidative stress are protagonists and age-related changes in other organs and tissues, such as ovaries, accentuate them.
MeSH term(s)	Aging/physiology ; Animals ; Bone Remodeling/physiology ; Bone and Bones/cytology ; Bone and Bones/physiopathology ; Estrogens/physiology ; Female ; Humans ; Male ; Osteoporosis/physiopathology ; Oxidative Stress/physiology ; Reactive Oxygen Species/pharmacology
Chemical Substances	Estrogens ; Reactive Oxygen Species
Language	English
Publishing date	2010-01-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	603096-8
ISSN	1945-7189 ; 0163-769X
ISSN (online)	1945-7189
ISSN	0163-769X
DOI	10.1210/er.2009-0024
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