Estradiol inhibits chondrogenic differentiation of mesenchymal stem cells via nonclassic signaling

Jenei-Lanzl, Zsuzsa; Straub, Rainer H.; Dienstknecht, Thomas; Huber, Michaela; Hager, Markus; Grässel, Susanne; Kujat, Richard; Angele, Martin K.; Nerlich, Michael; Angele, Peter

doi:10.1002/art.27328

Cited by 48 publications

(42 citation statements)

References 46 publications

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“…(30) While we cannot rule out the theoretical possibility of nontarget effects of the Neo cassette, the fact that others have observed similar effects on early osteoblast proliferation and suppression of chondrogenesis (proliferation was not specifically measured) using completely different systems gives us confidence in the fidelity of our results. (28,40) We should point out it also has been reported that the Cre-lox approach used by the other authors may result in unrecognized chromosomal rearrangements. (41) Whatever is the explanation for the phenotypic differences between the two models, it is clear from results of both groups that GPR30 is a critical receptor in regulation of the growth plate.…”

Section: Discussionmentioning

confidence: 88%

GPR30 deficiency causes increased bone mass, mineralization, and growth plate proliferative activity in male mice

Ford

Hajibeigi

Long

et al. 2010

Journal of Bone and Mineral Research

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Estrogen regulation of the male skeleton was first clearly demonstrated in patients with aromatase deficiency or a mutation in the ERα gene. Estrogen action on the skeleton is thought to occur mainly through the action of the nuclear receptors ERα and ERβ. Recently, in vitro studies have shown that the G protein–coupled receptor GPR30 is a functional estrogen receptor (ER). GPR30-deficient mouse models have been generated to study the in vivo function of this protein; however, its in vivo role in the male skeleton remains underexplored. We have characterized size, body composition, and bone mass in adult male Gpr30 knockout (KO) mice and their wild-type (WT) littermates. Gpr30 KO mice weighed more and had greater nasal-anal length (p < .001). Both lean mass and percent body fat were increased in the KO mice. Femur length was greater in Gpr30 KO mice, as was whole-body, spine, and femoral areal bone mineral density (p < .01). Gpr30 KO mice showed increased trabecular bone volume (p < .01) and cortical thickness (p < .001). Mineralized surface was increased in Gpr30 KO mice (p < .05). Bromodeoxyuridine (BrdU) labeling showed greater proliferation in the growth plate of Gpr30 KO mice (p < .05). Under osteogenic culture conditions, Gpr30 KO femoral bone marrow cells produced fewer alkaline phosphatase–positive colonies in early differentiating osteoblast cultures but showed increased mineralized nodule deposition in mature osteoblast cultures. Serum insulin-like growth factor 1 (IGF-1) levels were not different. These data suggest that in male mice, GPR30 action contributes to regulation of bone mass, size, and microarchitecture by a mechanism that does not require changes in circulating IGF-1. © 2011 American Society for Bone and Mineral Research.

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Section: Discussionmentioning

confidence: 88%

GPR30 deficiency causes increased bone mass, mineralization, and growth plate proliferative activity in male mice

Ford

Hajibeigi

Long

et al. 2010

Journal of Bone and Mineral Research

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“…6). Expression of the genes CYP24A1 and MMP13 has previously been reported to be activated by estrogens [57, 58]. Thus, it is tempting to speculate that repression of ERβ - knowing to act as an ERα antagonist in certain settings - might increase estrogen-triggered expression of MMP13 and CYP24A1 mediated by ERα.…”

Section: Discussionmentioning

confidence: 99%

Agonists and knockdown of estrogen receptor β differentially affect invasion of triple-negative breast cancer cells in vitro

Schüler-Toprak¹,

Haring²,

Inwald³

et al. 2016

BMC Cancer

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“…171 Although part of this effect is mediated through ERα and ERβ ,168 several avenues of research now suggest a role for GPER in bone and cartilage metabolism. In bone, GPER is expressed in osteocytes, osteoclasts and osteoblasts, 172,173 and is also detected in chondrocytes, 172,174 differentiation of which is regulated by GPER. 174 In addition, GPER expression also regulates bone growth, as illustrated by several models of GPER-deficiency, albeit in a sex-dependent manner.…”

Section: Gper In Physiology and Diseasementioning

confidence: 99%

“…In bone, GPER is expressed in osteocytes, osteoclasts and osteoblasts, 172,173 and is also detected in chondrocytes, 172,174 differentiation of which is regulated by GPER. 174 In addition, GPER expression also regulates bone growth, as illustrated by several models of GPER-deficiency, albeit in a sex-dependent manner. GPER deficieny inhibits bone growth in female mice; 77 similar results were reported in ovariectomized, estrogen-treated animals, 108 suggesting a role for GPER in estrogen-induced bone growth and development.…”

Section: Gper In Physiology and Diseasementioning

confidence: 99%

The G-protein-coupled estrogen receptor GPER in health and disease

2011

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Estrogens mediate profound effects throughout the body, and regulate physiological and pathological processes in both women and men. The decreased incidence of many diseases in premenopausal women is attributed to the presence of 17β-estradiol, the predominant and most potent endogenous estrogen. In addition to endogenous estrogens, however, several manmade and plant-derived molecules also exhibit estrogenic activity. Traditionally, the actions of 17β-estradiol are ascribed to two nuclear estrogen receptors (ERs), ERα and ERβ, which function as ligand-activated transcription factors. However, 17β-estradiol also mediates rapid signaling events via pathways that involve transmembrane ERs, such as G-protein-coupled ER 1, (GPER, formerly known as GPR30). In the past 10 years, GPER has been implicated in both rapid signaling and transcriptional regulation. With the discovery of GPER-selective ligands that can selectively modulate GPER function in cell experiments and preclinical studies, and the use of GPER-knockout mice, many more potential roles for GPER are currently being elucidated. This Review highlights the physiological roles of GPER in the reproductive, nervous, endocrine, immune and cardiovascular systems, as well as its pathological roles in a diverse array of disorders including cancer. GPER is emerging as a novel therapeutic target and prognostic indicator for these diseases.

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Estradiol inhibits chondrogenic differentiation of mesenchymal stem cells via nonclassic signaling

Cited by 48 publications

References 46 publications

GPR30 deficiency causes increased bone mass, mineralization, and growth plate proliferative activity in male mice

GPR30 deficiency causes increased bone mass, mineralization, and growth plate proliferative activity in male mice

Agonists and knockdown of estrogen receptor β differentially affect invasion of triple-negative breast cancer cells in vitro

The G-protein-coupled estrogen receptor GPER in health and disease

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