Downregulation of<b>beta</b>-catenin and transdifferentiation of human osteoblasts to adipocytes under estrogen deficiency

Foo, Clara J.; Frey, Sönke P.; Yang, Hee‐Young; Zellweger, René; Filgueira, Luis

doi:10.1080/09513590701556483

Cited by 26 publications

(21 citation statements)

References 31 publications

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“…This suggests that activation of β-catenin and its transport to the nucleus are facilitated by ERα, and that this receptor is pivotal for effi cient responsiveness to mechanical loading. Similar results were published by Foo et al [31], who found reduced expression of ERα and β-catenin in human osteoblasts when treated with fulvestrant, an estrogen receptor blocker.…”

Section: Lrp5supporting

confidence: 87%

WNT signaling in osteoarthritis and osteoporosis: What is the biological significance for the clinician?

Lodewyckx¹,

Lories

2009

Curr Rheumatol Rep

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Osteoporosis and osteoarthritis are common musculoskeletal disorders in which cause and outcome are determined by genetic and environmental factors. The WNT signaling pathway plays an important role in skeletal development and growth. Polymorphisms in a number of genes that belong to this pathway are associated with osteoarthritis and/or osteoporosis. This suggests a role for this molecular signaling pathway in postnatal joint and bone homeostasis and pathology. Increased activity of WNT signaling strengthens the bone but may have adverse effects on the articular cartilage. Frizzled related protein (FRZB) plays a role in both bone and cartilage. Better understanding of the WNT pathway and its modulators may lead to specific therapeutics for both osteoarthritis and osteoporosis. This review focuses on recent studies in human genetics and animal models and highlights the potential clinical relevance of this rapidly evolving field of research.

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Section: Lrp5supporting

confidence: 87%

WNT signaling in osteoarthritis and osteoporosis: What is the biological significance for the clinician?

Lodewyckx¹,

Lories

2009

Curr Rheumatol Rep

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“…Although mineralisation was not significantly different between the fulvestrant treated groups and the controls, both osteocalcin and osteopontin expression were significantly reduced in F1 at day 28. It has previously been shown that fulvestrant can reduce bone volume in rats [53] and treatment of human osteoblasts with fulvestrant in non-osteogenic conditions results in downregulation of estrogen receptor expression and can induce adipogenesis [45]. The results from the current study suggest that attachment of the fulvestrant molecule, an estrogen antagonist, to the osteoblast estrogen receptor is not sufficient to initiate an increase in mineralisation.…”

Section: Discussionmentioning

confidence: 41%

“…Fulvestrant is an analogue of estradiol which competes with endogenous estrogen for binding to the estrogen receptor [43] with a binding affinity that is 89% that of 17-β estradiol [44]. Previously fulvestrant has been used in vitro to mimic estrogen deficiency in human osteoblasts [45], however, the exact role of fulvestrant on osteoblast activity is unknown.…”

Section: Introductionmentioning

confidence: 99%

Estrogen Plus Estrogen Receptor Antagonists Alter Mineral Production by Osteoblasts In Vitro

2011

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ing in a decrease in whole bone and tissue biomechanical properties [ 5-9 ]. Interestingly, although osteoporosis reduces bone mass and structural strength, a recent study found that the remaining bone tissue is signifi cantly stronger and stiff er [ 10 ]. This unexpected fi nding has been corroborated to some extent by micro-CT studies which demonstrated an increase in the tissuelevel mineral content which was counter to the overall reduction in bone mineral density owing to a loss of bone mass [ 10 ]. More recent studies have provided further evidence of an increase in tissue mineral during osteoporosis [ 11 , 12 ]. Such changes may occur to compensate for bone loss, or alternatively these changes may occur prior to bone resorption and be causative. However, although it is intriguing to speculate on such events, it remains that the mechanisms by which an increase in mineralisation is initiated are unknown.

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“…As a specific example, researchers found that estrogen enhances canonical Wnt signaling pathway by preventing β-catenin from degradation and promoting its nuclear translocation. A physical interaction between ER and β-catenin has been found fundamental for the effect of estrogen on the Wnt/β-catenin pathway [48, 49]. The crosstalk between ERs and osteogenic signals not only promotes osteoblastogenesis, but also helps to prevent adipogenesis of bone marrow MSCs.…”

Section: Changed Bone Marrow Microenvironment Under Pathological Condmentioning

confidence: 99%

Osteoblast versus Adipocyte: Bone Marrow Microenvironment-Guided Epigenetic Control

Zuo

Zhang

et al. 2018

Case Rep Orthop Res

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The commitment and differentiation of bone marrow mesenchymal stem cells (MSCs) is tightly controlled by the local environment ensuring lineage differentiation balance and bone homeostasis. However, pathological conditions linked with osteoporosis have changed the bone marrow microenvironment, shifting MSCs’ fate to favor adipocytes over osteoblasts, and consequently leading to decreased bone mass with marrow fat accumulation. Multiple questions related to the underlying mechanisms remain to be answered. As recent findings have confirmed the fundamental role of the epigenetic mechanism in connecting environmental signals with gene expression and stem cell differentiation, a regulatory network in the bone marrow microenvironment, epigenetic modulation, gene expression, and MSC differentiation begins to emerge. This review discusses how pathological environmental factors affect MSCs’ fate by epigenetic modulating lineage-specific genes. We conclude that manipulating local environments and/or the epigenetic regulatory machinery that target the adipocyte differentiation pathway might be a therapeutic implication of bone loss diseases such as osteoporosis.

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Downregulation ofbeta-catenin and transdifferentiation of human osteoblasts to adipocytes under estrogen deficiency

Cited by 26 publications

References 31 publications

WNT signaling in osteoarthritis and osteoporosis: What is the biological significance for the clinician?

WNT signaling in osteoarthritis and osteoporosis: What is the biological significance for the clinician?

Estrogen Plus Estrogen Receptor Antagonists Alter Mineral Production by Osteoblasts In Vitro

Osteoblast versus Adipocyte: Bone Marrow Microenvironment-Guided Epigenetic Control

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