IGF-1 and bone: New discoveries from mouse models

Yakar, Shoshana; Courtland, Hayden William; Clemmons, David R.

doi:10.1002/jbmr.234

Cited by 122 publications

(87 citation statements)

References 100 publications

(65 reference statements)

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“…One of the interesting observations from the knockout of IGF-1 is the requirement of IGF-1 for parathyroid hormone (PTH) action on bone. 31 In the absence of IGF-1 (global-or osteoblast-specific deletion), PTH did not have a positive effect on the rate of bone formation. 42 In addition, it appears that PTH also needs IRS1 and not IRS2 for it to have the full anabolic effect on bone.…”

Section: Igf-1 and Osteoblastsmentioning

confidence: 93%

“…Additional studies that have used inducible liverspecific IGF-1-deficient mice to tease out the effects of serum IGF-1 at different time points, found that depleting serum IGF-1 at 4 weeks in male mice led to a decrease in both trabecular and cortical bone by 16 weeks, deletion of serum IGF-1 at 8 weeks of age affected only the cortical bone at 32 weeks, whereas depletion after peak bone accretion did not have detrimental effects on bone. 31,37 These studies show that serum IGF-1 has an important role in skeletal development and maintenance.…”

Section: Igf-1 and Chondrocytesmentioning

confidence: 97%

“…30 Chondrocytes in the long bones express IGF1R and also secrete IGF-1, global deletion of IGF-1 and its receptor IGF1R leads to both skeletal defects and cartilage changes including reduced bone length. 31 A chondrocyte-specific IGF-1 knockout has been described by using Igf-1 flox/flox mice that were crossed to a collagen2a1 (Col2a1)-specific cre (chondrocyte-specific cre). The results revealed that loss of IGF-1 produced by these collagen2-expressing chondrocytes led to changes in the longitudinal growth and width of bone as well as a decrease in bone mineral density.…”

Section: Igf-1 and Chondrocytesmentioning

confidence: 99%

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IGF-1 regulation of key signaling pathways in bone

2013

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Insulin-like growth factor 1 (IGF-1) is an unique peptide that functions in an endocrine/paracrine and autocrine manner in most tissues. Although it was postulated initially that liver-derived IGF-1 was the major source of IGF-1 (that is, the somatomedin hypothesis), it is also produced in a wide variety of tissues and can function in numerous ways as both a proliferative and differentiative factor. One such tissue is bone and all cell lineages in the skeleton have been shown to not only require IGF-1 for normal development and function but also to respond to IGF-1 via the IGF-1 receptor. Ligandreceptor activation leads to several distinct downstream signaling cascades, which have significant implications for cell survival, protein synthesis and energy utilization. The novel role of IGF-1 in regulating metabolic demands of the bone remodeling unit is currently under investigation. More studies are likely to shed new light on various aspects of skeletal physiology and potentially may lead to new therapeutics.

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Section: Igf-1 and Osteoblastsmentioning

confidence: 93%

Section: Igf-1 and Chondrocytesmentioning

confidence: 97%

Section: Igf-1 and Chondrocytesmentioning

confidence: 99%

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IGF-1 regulation of key signaling pathways in bone

2013

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“…As shown in revealed that the fetal mice demonstrated short-limb dwarfism delays in mineralization and increased chondrocyte apoptosis 25) .…”

Section: Expression Of Igf-1 and P-akt Proteinmentioning

confidence: 91%

Phosphoinositide 3-Kinase (PI3K) Activation is Differentially Regulated during Osteogenesis induced by TGF-β1 and BMP-2/BMP-7

Yamashita

Ochiai

Saito

et al. 2014

J. Hard Tissue Biology.

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Periodontal ligament (PDL) cells are comprised of heterogenous cell populations including mesenchymal stem cells and osteogenic progenitor cells. We previously reported that differentiation of human PDL cells into osteoblasts requires phosphoinositide 3-kinase (PI3K) activities. Here, we investigate osteoblast differentiation using TGF-1, BMP-2/BMP-7, and dexamethasone (Dex) in human PDL cells, focusing on the PI3K/Akt pathway. We found that in TGF-1-treated cells, Dex increased IGF-1 expression as well as phosphorylated Akt, which is a main target molecule of PI3K. Downregulation of IGF-1 expression and enhanced phosphorylation of Akt were observed in BMPs with Dex-treated cells, even though alkaline phosphatase expression and activities were enhanced. These results indicate that IGF-1 is a key regulator in TGF-1-induced osteogenesis, but it is not required in osteoblast differentiation initiated by BMPs. Because BMPs require PI3K activation for osteoblast differentiation, and because BMP treatment upregulates Akt phosphorylation, signaling molecules other than IGF-1 may support BMP-induced osteoblast differentiation.

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“…However, autocrine/paracrine IGF-1 action stimulates bone cell activity and consequently increases bone formation (Yakar and Rosen, 2003). Mouse strains with higher IFG-1 levels have higher BMD and cortical thickness (Yakar et al, 2010). Protein restriction in rats reduces serum IGF-1 and impairs cortical bone formation (Bourrin et al, 2000).…”

Section: Igf-1 In Ca Metabolismmentioning

confidence: 99%

Review of Ca Metabolic Studies and a Model for Optimizing Gastrointestinal Ca Absorption and Peak Bone Mass in Adolescents

Park

Cho

Lee

2015

Journal of Biosystems Engineering

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Purpose:The objective of this study is to review researches regarding factors that potentially affect adolescent calcium (Ca) metabolism, and to suggest a potential modeling approach for optimizing gastrointestinal Ca absorption and peak bone mass. Background: Optimal gastrointestinal Ca absorption is a key to maximizing peak bone mass in adolescents. Urine Ca excretion in adolescents rises only after bone accretion is saturated, indicating that higher intestinal Ca absorption and bone retention is necessary to ensure maximum bone accretion. Hence, maximizing peak bone mass is possible by controlling the factors influencing gastrointestinal Ca absorption and bone accretion. However, a mechanism that explains the unique adolescent Ca metabolism has not yet been elucidated. Review: Dietary factors that enhance gastrointestinal Ca absorption may increase the available Ca pool usable for bone accretion, and a specific hormone may direct optimal Ca utilization to maximize peak bone mass. IGF-1 is an endocrine hormone whose levels peak during adolescence and increase fractional Ca absorption and bone Ca accretion. Prebiotics, generally obtained from dietary sources, have been reported to exert a beneficial effect on Ca absorption via microbiota activity. We selected and reviewed three candidates that could be used to propose a comprehensive Ca metabolic model for optimal Ca absorption and peak bone mass in adolescents. Modeling: Modeling has been used to investigate Ca metabolism and its regulators. Herein, we reviewed previous Ca modeling studies. Based on this review, we proposed a method for developing a comprehensive model that includes regulatory effectors of IGF-1 and prebiotics.

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IGF-1 and bone: New discoveries from mouse models

Cited by 122 publications

References 100 publications

IGF-1 regulation of key signaling pathways in bone

IGF-1 regulation of key signaling pathways in bone

Phosphoinositide 3-Kinase (PI3K) Activation is Differentially Regulated during Osteogenesis induced by TGF-β1 and BMP-2/BMP-7

Review of Ca Metabolic Studies and a Model for Optimizing Gastrointestinal Ca Absorption and Peak Bone Mass in Adolescents

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