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Article ; Online: International meeting on GH/IGF actions in the shadow of COVID19.

Yakar, Shoshana

2020 Volume 23, Issue Suppl 1, Page(s) 1

MeSH term(s)	COVID-19 ; Growth Hormone ; Humans ; Insulin-Like Growth Factor I ; SARS-CoV-2 ; Signal Transduction
Chemical Substances	Insulin-Like Growth Factor I (67763-96-6) ; Growth Hormone (9002-72-6)
Keywords	covid19
Language	English
Publishing date	2020-10-31
Publishing country	United States
Document type	Editorial
ZDB-ID	1385151-2
ISSN	1573-7403 ; 1386-341X
ISSN (online)	1573-7403
ISSN	1386-341X
DOI	10.1007/s11102-020-01098-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: International meeting on GH/IGF actions in the shadow of COVID19

Yakar, Shoshana

Pituitary

Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #893320
Database	COVID19

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Article: Development of primary osteoarthritis during aging in genetically diverse UM-HET3 mice.

Poudel, Sher Bahadur / Ruff, Ryan R / Yildirim, Gozde / Miller, Richard A / Harrison, David E / Strong, Randy / Kirsch, Thorsten / Yakar, Shoshana

bioRxiv : the preprint server for biology

2024

Abstract: This study investigated the prevalence and progression of primary osteoarthritis (OA) in aged UM-HET3 mice. Using the Osteoarthritis Research Society International (OARSI) scoring system, we assessed articular cartilage (AC) integrity in 182 knee joints ... ...

Abstract	This study investigated the prevalence and progression of primary osteoarthritis (OA) in aged UM-HET3 mice. Using the Osteoarthritis Research Society International (OARSI) scoring system, we assessed articular cartilage (AC) integrity in 182 knee joints of 22-25 months old mice. Aged UM-HET3 mice showed a high prevalence of primary OA in both sexes. Significant positive correlations were found between cumulative AC (cAC) scores and synovitis in both sexes, and osteophyte formation in female mice. Ectopic chondrogenesis did not show significant correlations with cAC scores. Significant direct correlations were found between AC scores and inflammatory markers in chondrocytes, including matrix metalloproteinase-13 (MMP-13), inducible nitric oxide synthase (iNOS), and the NLR family pyrin domain containing-3 (NLRP3) inflammasome in both sexes, indicating a link between OA severity and inflammation. Additionally, markers of cell cycle arrest, such as p16 and β-galactosidase, also correlated with AC scores. Using micro-CT, we examined the correlations between subchondral bone (SCB) morphology traits and AC scores. In male mice, no significant correlations were found between SCB morphology traits and cAC scores, while in female mice, significant correlations were found between cAC scores and tibial SCB plate bone mineral density. Finally, we explored the effects of methylene blue (MB) and mitoquinone (MitoQ), two agents that affect mitochondrial function, on the prevalence and progression of OA during aging. Notably, MB and MitoQ treatments influenced the disease's progression in a sex-specific manner. MB treatment significantly reduced cAC scores at the medial knee joint, while MitoQ treatment reduced cAC scores, but these did not reach significance. In conclusion, our study provides comprehensive insights into the prevalence and progression of primary OA in aged UM-HET3 mice, highlighting the sex-specific effects of MB and MitoQ treatments. The correlations between AC scores and various pathological factors underscore the multifaceted nature of OA and its association with inflammation and subchondral bone changes.
Language	English
Publishing date	2024-01-14
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.12.16.571693
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: A systematic review and meta-analysis on the efficacy of stem cell therapy on bone brittleness in mouse models of osteogenesis imperfecta.

Battle, Lauren / Yakar, Shoshana / Carriero, Alessandra

Bone reports

2021 Volume 15, Page(s) 101108

Abstract: There is no cure for osteogenesis imperfecta (OI), and current treatments can only partially correct the bone phenotype. Stem cell therapy holds potential to improve bone quality and quantity in OI. Here, we conduct a systematic review and meta-analysis ... ...

Abstract	There is no cure for osteogenesis imperfecta (OI), and current treatments can only partially correct the bone phenotype. Stem cell therapy holds potential to improve bone quality and quantity in OI. Here, we conduct a systematic review and meta-analysis of published studies to investigate the efficacy of stem cell therapy to rescue bone brittleness in mouse models of OI. Identified studies included bone marrow, mesenchymal stem cells, and human fetal stem cells. Effect size of fracture incidence, maximum load, stiffness, cortical thickness, bone volume fraction, and raw engraftment rates were pooled in a random-effects meta-analysis. Cell type, cell number, injection route, mouse age, irradiation, anatomical bone, and follow up time were considered as moderators. It was not possible to investigate further parameters due to the lack of standards of investigation between the studies. Despite the use of
Language	English
Publishing date	2021-07-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2821774-3
ISSN	2352-1872
ISSN	2352-1872
DOI	10.1016/j.bonr.2021.101108
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Development of primary osteoarthritis during aging in genetically diverse UM-HET3 mice.

Poudel, Sher Bahadur / Ruff, Ryan R / Yildirim, Gozde / Miller, Richard A / Harrison, David E / Strong, Randy / Kirsch, Thorsten / Yakar, Shoshana

Research square

2024

Abstract: Background: Primary osteoarthritis (OA) occurs without identifiable underlying causes such as previous injuries or specific medical conditions. Age is a major contributing factor to OA, and as one ages, various joint tissues undergo gradual change, ... ...

Abstract	Background: Primary osteoarthritis (OA) occurs without identifiable underlying causes such as previous injuries or specific medical conditions. Age is a major contributing factor to OA, and as one ages, various joint tissues undergo gradual change, including degeneration of the articular cartilage, alterations in subchondral bone (SCB) morphology, and inflammation of the synovium. Methods: We investigated the prevalence of primary OA in aged, genetically diverse UM-HET3 mice. Articular cartilage (AC) integrity and SCB morphology were assessed in 182 knee joints of 22-25 months old mice using the Osteoarthritis Research Society International (OARSI) scoring system and micro-CT, respectively. Additionally, we explored the effects of methylene blue (MB) and mitoquinone (MitoQ), two agents that affect mitochondrial function, on the prevalence and progression of OA during aging. Results: Aged UM-HET3 mice showed a high prevalence of primary OA in both sexes. Significant positive correlations were found between cumulative AC (cAC) scores and synovitis in both sexes, and osteophyte formation in female mice. Ectopic chondrogenesis did not show significant correlations with cAC scores. Significant direct correlations were found between AC scores and inflammatory markers in chondrocytes, including matrix metalloproteinase-13, inducible nitric oxide synthase, and the NLR family pyrin domain containing-3 inflammasome in both sexes, indicating a link between OA severity and inflammation. Additionally, markers of cell cycle arrest, such as p16 and β-galactosidase, also correlated with AC scores. In male mice, no significant correlations were found between SCB morphology traits and cAC scores, while in female mice, significant correlations were found between cAC scores and tibial SCB plate bone mineral density. Notably, MB and MitoQ treatments influenced the disease's progression in a sex-specific manner. MB treatment significantly reduced cAC scores at the medial knee joint, while MitoQ treatment reduced cAC scores, but these did not reach significance. Conclusions: Our study provides comprehensive insights into the prevalence and progression of primary OA in aged UM-HET3 mice, highlighting the sex-specific effects of MB and MitoQ treatments. The correlations between AC scores and various pathological factors underscore the multifaceted nature of OA and its association with inflammation and subchondral bone changes.
Language	English
Publishing date	2024-01-22
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-3858256/v1
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Effects of GH/IGF axis on bone and cartilage

Dixit, Manisha / Poudel, Sher Bahadur / Yakar, Shoshana

Molecular and cellular endocrinology. 2021 Jan. 01, v. 519

2021

Abstract: Growth hormone (GH) and its mediator, the insulin-like growth factor-1 (IGF-1) regulate somatic growth, metabolism and many aspects of aging. As such, actions of GH/IGF have been studied in many tissues and organs over decades. GH and IGF-1 are part of ... ...

Abstract	Growth hormone (GH) and its mediator, the insulin-like growth factor-1 (IGF-1) regulate somatic growth, metabolism and many aspects of aging. As such, actions of GH/IGF have been studied in many tissues and organs over decades. GH and IGF-1 are part of the hypothalamic/pituitary somatotrophic axis that consists of many other regulatory hormones, receptors, binding proteins, and proteases. In humans, GH/IGF actions peak during pubertal growth and regulate skeletal acquisition through stimulation of extracellular matrix production and increases in bone mineral density. During aging the activity of these hormones declines, a state called somatopaguss, which associates with deleterious effects on the musculoskeletal system. In this review, we will focus on GH/IGF-1 action in bone and cartilage. We will cover many studies that have utilized congenital ablation or overexpression of members of this axis, as well as cell-specific gene-targeting approaches used to unravel the nature of the GH/IGF-1 actions in the skeleton in vivo.
Keywords	bone density ; cartilage ; extracellular matrix ; gene targeting ; insulin-like growth factor I ; metabolism ; proteinases ; skeleton ; somatotropin
Language	English
Dates of publication	2021-0101
Publishing place	Elsevier B.V.
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	187438-x
ISSN	1872-8057 ; 0303-7207
ISSN (online)	1872-8057
ISSN	0303-7207
DOI	10.1016/j.mce.2020.111052
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Effects of GH/IGF axis on bone and cartilage.

Dixit, Manisha / Poudel, Sher Bahadur / Yakar, Shoshana

Molecular and cellular endocrinology

2020 Volume 519, Page(s) 111052

Abstract	Growth hormone (GH) and its mediator, the insulin-like growth factor-1 (IGF-1) regulate somatic growth, metabolism and many aspects of aging. As such, actions of GH/IGF have been studied in many tissues and organs over decades. GH and IGF-1 are part of the hypothalamic/pituitary somatotrophic axis that consists of many other regulatory hormones, receptors, binding proteins, and proteases. In humans, GH/IGF actions peak during pubertal growth and regulate skeletal acquisition through stimulation of extracellular matrix production and increases in bone mineral density. During aging the activity of these hormones declines, a state called somatopaguss, which associates with deleterious effects on the musculoskeletal system. In this review, we will focus on GH/IGF-1 action in bone and cartilage. We will cover many studies that have utilized congenital ablation or overexpression of members of this axis, as well as cell-specific gene-targeting approaches used to unravel the nature of the GH/IGF-1 actions in the skeleton in vivo.
MeSH term(s)	Animals ; Bone Development ; Bone and Bones/metabolism ; Cartilage/metabolism ; Growth Hormone/metabolism ; Humans ; Insulin-Like Growth Factor I/metabolism ; Osteoarthritis/metabolism ; Osteoarthritis/pathology
Chemical Substances	Insulin-Like Growth Factor I (67763-96-6) ; Growth Hormone (9002-72-6)
Language	English
Publishing date	2020-10-14
Publishing country	Ireland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	187438-x
ISSN	1872-8057 ; 0303-7207
ISSN (online)	1872-8057
ISSN	0303-7207
DOI	10.1016/j.mce.2020.111052
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Article ; Online: Targeting mitochondrial dysfunction using methylene blue or mitoquinone to improve skeletal aging.

Poudel, Sher Bahadur / Frikha-Benayed, Dorra / Ruff, Ryan R / Yildirim, Gozde / Dixit, Manisha / Korstanje, Ron / Robinson, Laura / Miller, Richard A / Harrison, David E / Strong, John R / Schaffler, Mitchell B / Yakar, Shoshana

Aging

2024 Volume 16, Issue 6, Page(s) 4948–4964

Abstract: Methylene blue (MB) is a well-established antioxidant that has been shown to improve mitochondrial function in ... ...

Abstract	Methylene blue (MB) is a well-established antioxidant that has been shown to improve mitochondrial function in both
MeSH term(s)	Male ; Female ; Mice ; Animals ; Antioxidants/pharmacology ; Methylene Blue/pharmacology ; Mice, Inbred C57BL ; Oxidative Stress ; Aging ; Mitochondrial Diseases ; Organophosphorus Compounds ; Ubiquinone/analogs & derivatives
Chemical Substances	mitoquinone (47BYS17IY0) ; Antioxidants ; Methylene Blue (T42P99266K) ; Organophosphorus Compounds ; Ubiquinone (1339-63-5)
Language	English
Publishing date	2024-03-25
Publishing country	United States
Document type	Journal Article
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.205147
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Regulation of skeletal growth and mineral acquisition by the GH/IGF-1 axis: Lessons from mouse models.

Yakar, Shoshana / Isaksson, Olle

Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society

2016 Volume 28, Page(s) 26–42

Abstract: The growth hormone (GH) and its downstream mediator, the insulin-like growth factor-1 (IGF-1), construct a pleotropic axis affecting growth, metabolism, and organ function. Serum levels of GH/IGF-1 rise during pubertal growth and associate with peak bone ...

Abstract	The growth hormone (GH) and its downstream mediator, the insulin-like growth factor-1 (IGF-1), construct a pleotropic axis affecting growth, metabolism, and organ function. Serum levels of GH/IGF-1 rise during pubertal growth and associate with peak bone acquisition, while during aging their levels decline and associate with bone loss. The GH/IGF-1 axis was extensively studied in numerous biological systems including rodent models and cell cultures. Both hormones act in an endocrine and autocrine/paracrine fashion and understanding their distinct and overlapping contributions to skeletal acquisition is still a matter of debate. GH and IGF-1 exert their effects on osteogenic cells via binding to their cognate receptor, leading to activation of an array of genes that mediate cellular differentiation and function. Both hormones interact with other skeletal regulators, such as sex-steroids, thyroid hormone, and parathyroid hormone, to facilitate skeletal growth and metabolism. In this review we summarized several rodent models of the GH/IGF-1 axis and described key experiments that shed new light on the regulation of skeletal growth by the GH/IGF-1 axis.
Language	English
Publishing date	2016-06
Publishing country	Scotland
Document type	Journal Article
ZDB-ID	1436781-6
ISSN	1532-2238 ; 1096-6374
ISSN (online)	1532-2238
ISSN	1096-6374
DOI	10.1016/j.ghir.2015.09.004
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Article ; Online: Insulin-like growth factors: actions on the skeleton.

Yakar, Shoshana / Werner, Haim / Rosen, Clifford J

Journal of molecular endocrinology

2018 Volume 61, Issue 1, Page(s) T115–T137

Abstract: The discovery of the growth hormone (GH)-mediated somatic factors (somatomedins), insulin-like growth factor (IGF)-I and -II, has elicited an enormous interest primarily among endocrinologists who study growth and metabolism. The advancement of molecular ...

Abstract	The discovery of the growth hormone (GH)-mediated somatic factors (somatomedins), insulin-like growth factor (IGF)-I and -II, has elicited an enormous interest primarily among endocrinologists who study growth and metabolism. The advancement of molecular endocrinology over the past four decades enables investigators to re-examine and refine the established somatomedin hypothesis. Specifically, gene deletions, transgene overexpression or more recently, cell-specific gene-ablations, have enabled investigators to study the effects of the
MeSH term(s)	Animals ; Chondrocytes/metabolism ; Humans ; Osteoblasts/metabolism ; Osteoclasts/metabolism ; Skeleton/metabolism ; Somatomedins/metabolism
Chemical Substances	Somatomedins
Language	English
Publishing date	2018-04-06
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	645012-x
ISSN	1479-6813 ; 0952-5041
ISSN (online)	1479-6813
ISSN	0952-5041
DOI	10.1530/JME-17-0298
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