Insulin-Like Growth Factor Binding Protein-5 Interacts with the Vitamin D Receptor and Modulates the Vitamin D Response in Osteoblasts

Schedlich, Lynette J.; Muthukaruppan, Anita; O’Han, Michelle K.; Baxter, Robert C.

doi:10.1210/me.2006-0558

Cited by 66 publications

(46 citation statements)

References 33 publications

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“…As shown in Supplementary Fig. S1, different genes involved in osteogenic differentiation are upregulated in ATP-treated BM-hMSCs compared to the untreated sample, such as osteoblastic transcription factors (ie, RUNX2 [38] and FOXO1 [39]), osteoblastic markers (ie, ANKH, BGLAP, and SPP1 [40,41]), and osteogenic growth factors (ie, BMP2, BMP6, WISP2, and IGFBP5 [42][43][44][45]). Moreover, ATP treatment of BM-hMSCs increased the expression of adipogenic transcription factors (ie, CEBPA, PPARGC1A, and CEBPB) [46] and adipocytespecific proteins (ie, ADFP, PC, and SPG20 [47][48][49]) (Supplementary Fig.…”

Section: Gene Expression Profile Of Atp-treated Undifferentiated Bm-hmentioning

confidence: 97%

Extracellular Purines Promote the Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells to the Osteogenic and Adipogenic Lineages

Ciciarello

Zini

Rossi

et al. 2013

Stem Cells and Development

102

101

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Extracellular nucleotides are potent signaling molecules mediating cell-specific biological functions, mostly within the processes of tissue damage and repair and flogosis. We previously demonstrated that adenosine 5¢-triphosphate (ATP) inhibits the proliferation of human bone marrow-derived mesenchymal stem cells (BMhMSCs), while stimulating, in vitro and in vivo, their migration. Here, we investigated the effects of ATP on BM-hMSC differentiation capacity. Molecular analysis showed that ATP treatment modulated the expression of several genes governing adipogenic and osteoblastic (ie, WNT-pathway-related genes) differentiation of MSCs. Functional studies demonstrated that ATP, under specific culture conditions, stimulated adipogenesis by significantly increasing the lipid accumulation and the expression levels of the adipogenic master gene PPARc (peroxisome proliferator-activated receptor-gamma). In addition, ATP stimulated osteogenic differentiation by promoting mineralization and expression of the osteoblast-related gene RUNX2 (runt-related transcription factor 2). Furthermore, we demonstrated that ATP stimulated adipogenesis via its triphosphate form, while osteogenic differentiation was induced by the nucleoside adenosine, resulting from ATP degradation induced by CD39 and CD73 ectonucleotidases expressed on the MSC membrane. The pharmacological profile of P2 purinergic receptors (P2Rs) suggests that adipogenic differentiation is mainly mediated by the engagement of P2Y1 and P2Y4 receptors, while stimulation of the P1R adenosine-specific subtype A2B is involved in adenosine-induced osteogenic differentiation. Thus, we provide new insights into molecular regulation of MSC differentiation.

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Section: Gene Expression Profile Of Atp-treated Undifferentiated Bm-hmentioning

confidence: 97%

Extracellular Purines Promote the Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells to the Osteogenic and Adipogenic Lineages

Ciciarello

Zini

Rossi

et al. 2013

Stem Cells and Development

102

101

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“…This IGFBP-3 effect involved the rapid mitochondrial translocation of RXRα-Nur77 dimers, resulting in cytochtome c release, and required direct cytoplasmic interaction between IGFBP-3 and Nur77 (Lee, et al 2007), but the precise details of the mechanism are still unclear. IGFBP-3 also binds directly to VDR, as does the related binding protein IGFBP-5 (Schedlich, et al 2007b), and IGFBP-3 is inhibitory to VDR transcriptional activity (Ikezoe et al 2004).…”

Section: Nuclear Hormone Receptorsmentioning

confidence: 99%

Insulin-like growth factor binding protein-3 (IGFBP-3): Novel ligands mediate unexpected functions

Baxter

2013

J. Cell Commun. Signal.

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In addition to its important role in the regulation of somatic growth by acting as the major circulating transport protein for the insulin-like growth factors (IGFs), IGF binding protein-3 (IGFBP-3) has a variety of intracellular ligands that point to its function within major signaling pathways. The discovery of its interaction with the retinoid X receptor has led to the elucidation of roles in regulating the function of several nuclear hormone receptors including retinoic acid receptor-α, Nur77 and vitamin D receptor. Its interaction with the nuclear hormone receptor peroxisome proliferator-activated receptor-γ is believed to be involved in regulating adipocyte differentiation, which is also modulated by IGFBP-3 through an interaction with TGFβ/Smad signaling. IGFBP-3 can induce apoptosis alone or in conjunction with other agents, and in different systems can activate caspases −8 and −9. At least two unrelated proteins (LRP1 and TMEM219) have been designated as receptors for IGFBP-3, the latter with a demonstrated role in inducing caspase-8-dependent apoptosis. In contrast, IGFBP-3 also has demonstrated roles in survival-related functions, including the repair of DNA double-strand breaks through interaction with the epidermal growth factor receptor and DNAdependent protein kinase, and the induction of autophagy through interaction with GRP78. The ability of IGFBP-3 to modulate the balance between pro-apoptotic and prosurvival sphingolipids by regulating sphingosine kinase 1 and sphingomyelinases may be integral to its role at the crossroads between cell death and survival in response to a variety of stimuli. The pleiotropic nature of IGFBP-3 activity supports the idea that IGFBP-3 itself, or pathways with which it interacts, should be investigated as targets of therapy for a variety of diseases.

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“…Within the nucleus, IGFBP-5 had transactivation activity via 492 its N-terminal domain (Zhao, et al 2006) and it bound transcription factors such as FHL2 (Amaar, 493 et al 2002) and the nucleolar protein nucleolin (Su, et al 2015). Nuclear IGFBP-5 bound to the 494 vitamin D receptor and attenuated vitamin D-induced expression of bone differentiation markers 495 (Schedlich, et al 2007). However, nuclear translocation and nucleolin binding were not required for 496 IGFBP-5-induced fibrosis (Su et al 2015).…”

mentioning

confidence: 99%

40 YEARS OF IGF1: IGF-binding proteins

Bach

2018

Journal of Molecular Endocrinology

204

111

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Insulin-like growth factor binding proteins (IGFBPs) 1-6 bind IGFs but not insulin with high affinity. They were initially identified as serum carriers and passive inhibitors of IGF actions.However, subsequent studies showed that, although IGFBPs inhibit IGF actions in many circumstances, they may also potentiate these actions. IGFBPs are widely expressed in most tissues, and they are flexible endocrine and autocrine/paracrine regulators of IGF activity, which is essential for this important physiological system. More recently, individual IGFBPs have been shown to have IGF-independent actions. Mechanisms underlying these actions include (i) interaction with non-IGF proteins in compartments including the extracellular space and matrix, the cell surface and intracellularly; (ii) interaction with and modulation of other growth factor pathways including EGF, TGF-β and VEGF; and (iii) direct or indirect transcriptional effects following nuclear entry of IGFBPs. Through these IGF-dependent and IGF-independent actions, IGFBPs modulate essential cellular processes including proliferation, survival, migration, senescence, autophagy and angiogenesis. They have been implicated in a range of disorders including malignant, metabolic, neurological and immune diseases. A more complete understanding of their cellular roles may lead to the development of novel IGFBP-based therapeutic opportunities.Page 2 of 51 3The somatomedin hypothesis, which postulated that growth hormone activity was mediated by a 1 serum factor, was published in 1957 (Salmon and Daughaday 1957). In the 1960s, several 2 circulating somatomedin activities were identified and attributed to peptides sized 5~8 kDa that had 3 both growth promoting and insulin-like metabolic effects. A paradox of these early observations 4 was that normoglycaemia was maintained in vivo despite the circulating concentrations of 5 somatomedins being sufficient to cause profound hypoglycaemia. Following the purification of 6 these small somatomedin peptides, it was observed that almost all of the circulating somatomedin 7 activity was found in a number of chromatographic peaks with apparent molecular weights greater 8 than 30~40 kDa and further studies indicated that this was due to binding by plasma binding 9proteins (Hintz and Liu 1977;Megyesi, et al. 1975;Zapf, et al. 1975). The apparent hypoglycaemia 10 paradox could then be resolved if somatomedin activity was inhibited by association with these 11 binding proteins. Of note, these early studies already demonstrated that insulin did not bind to these 12 proteins. 13 14In the following years, the somatomedin activities were identified as IGF-I and IGF-II, and they 15 were sequenced and cloned. IGF binding proteins (IGFBPs) 1-3 were the first to be identified and 16 purified, with IGFBPs 4-6 being subsequently described (Rajaram, et al. 1997;Rechler 1993). By 17 the early 1990s, all six members of this high affinity IGFBP family had been cloned and a number 18 of key structural and sequence similarities identified. Addition...

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Insulin-Like Growth Factor Binding Protein-5 Interacts with the Vitamin D Receptor and Modulates the Vitamin D Response in Osteoblasts

Cited by 66 publications

References 33 publications

Extracellular Purines Promote the Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells to the Osteogenic and Adipogenic Lineages

Extracellular Purines Promote the Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells to the Osteogenic and Adipogenic Lineages

Insulin-like growth factor binding protein-3 (IGFBP-3): Novel ligands mediate unexpected functions

40 YEARS OF IGF1: IGF-binding proteins

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