Bone Morphogenetic Protein-7 (OP1) and Transforming Growth Factor-β1 Modulate 1,25(OH)2-Vitamin D3-Induced Differentiation of Human Osteoblasts

Eichner, Annegret; Brock, Josef; Heldin, Carl‐Henrik; Souchelnytskyi, Serhiy

doi:10.1006/excr.2002.5488

Cited by 18 publications

(13 citation statements)

References 35 publications

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“…Third, expression of Smad6 in mesangial cells consistently and significantly enhanced Smad3-dependent transcriptional activity induced by TGF-␤. Interestingly, bone morphogenetic protein 7 (BMP7) is an essential regulator of kidney development (41) that is known to oppose TGF-␤ signaling (42) and ameliorate renal fibrogenesis induced by ureteral obstruction (43). Smad6 is an efficient inhibitor of BMP signaling; it is therefore possible that TGF-␤ induces Smad6 in mesangial cells to downmodulate negative cross-regulation by BMP-7, resulting in indirect enhancement of TGF-␤/Smad signaling in the injured mesangium.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Smads and TGF-β Signaling in Glomerular Cells

Schiffer¹,

Schiffer²,

Gupta³

et al. 2002

Journal of the American Society of Nephrology

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ABSTRACT. Smad6 and Smad7 are inhibitory SMADs with putative functional roles at the intersection of major intracellular signaling networks, including TGF-β, receptor tyrosine kinase (RTK), JAK/STAT, and NF-κB pathways. This study reports differential functional roles and regulation of Smad6 and Smad7 in TGF-β signaling in renal cells, in murine models of renal disease and in human glomerular diseases. Smad7 is upregulated in podocytes in all examined glomerular diseases (focal segmental glomerulosclerosis [FSGS], minimal-change disease [MCD], membranous nephropathy [MNP], lupus nephritis [LN], and diabetic nephropathy [DN]) with a statistically significant upregulation in “classical” podocyte-diseases such as FSGS and MCD. TGF-β induces Smad7 synthesis in cultured podocytes and Smad6 synthesis in cultured mesangial cells. Although Smad7 expression inhibited both Smad2- and Smad3-mediated TGF-β signaling in podocytes, it inhibited only Smad3 but not Smad2 signaling in mesangial cells. In contrast, Smad6 had no effect on TGF-β/Smad signaling in podocytes and enhanced Smad3 signaling in mesangial cells. These data suggest that Smad7 is activated in injured podocytes in vitro and in human glomerular disease and participates in negative control of TGF-β/Smad signaling in addition to its pro-apoptotic activity, whereas Smad6 has no role in TGF-β response and injury in podocytes. In contrast, Smad6 is upregulated in the mesangium in human glomerular diseases and may be involved in functions independent of TGF-β/Smad signaling. These data indicate an important role for Smad6 and Smad7 in glomerular cells in vivo that could be important for the cell homeostasis in physiologic and pathologic conditions.

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Section: Discussionmentioning

confidence: 99%

Inhibitory Smads and TGF-β Signaling in Glomerular Cells

Schiffer¹,

Schiffer²,

Gupta³

et al. 2002

Journal of the American Society of Nephrology

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“…This suggests that the synergistic enhancement of ALP activity was due to the modulation of a 1,25(OH) 2 D 3 -induced differentiation effect by PRP-1.09 rather than vice versa. Numerous studies have suggested that 1,25(OH) 2 D 3 interacts with various growth factors and cytokines to mediate its effects in coordinating cell growth and differentiation (Wergedal et al 1992;Ingram et al 1994;Liu et al 1999;Eichner et al 2002). Based on these reports, three possible mechanisms explaining the modulation of 1,25(OH) 2 D 3 action by PRP can be advanced: (1) growth factors and cytokines in PRP upregulate the number of 1,25(OH) 2 D 3 receptors; (2) growth factors and cytokines in PRP affects expression of the Fos and Jun proteins which can heterodimerize and bind to vitamin D response element sequences; or (3) growth factors and cytokines in PRP increase 1,25(OH) 2 D 3 receptor phosphorylation, resulting in transactivation of gene transcription.…”

Section: Prp Stimulates Hmsc Proliferation In Dose-response Modementioning

confidence: 99%

Platelet-rich plasma and 1,25(OH)2 vitamin D3 synergistically stimulate osteogenic differentiation of adult human mesenchymal stem cells

et al. 2010

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Mesenchymal stem cell proliferation and differentiation are regulated by growth factors and systemic hormones in a concerted manner. We have examined the effects of platelet-rich plasma (PRP) and its interaction with 1,25(OH)(2) vitamin D(3) [1,25(OH)(2)D(3)] on the differentiation and proliferation of human mesenchymal stem cells (hMSCs). PRP stimulated cell proliferation in a manner inversely proportional to the dose. Exposure to PRP inhibited hMSC osteogenic differentiation. Co-treatment with PRP and 1,25(OH)(2)D(3), however, synergistically stimulated osteogenic differentiation. Serial co-treatment with PRP and 1,25(OH)(2)D(3) showed that this synergistic effect was due to the modulation of a 1,25(OH)(2)D(3)-induced differentiation by PRP rather than vice versa.

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“…42,43 BMP7 expression in the absence of vitamin D induces osteoblast differentiation and mineralization, but this effect is reversed in the presence of 1-25(OH) 2 vitamin D 3 . 44 Thus, it is possible that variation in BMP7 is important for osteonecrosis risk in younger but not older children due to age related differences in vitamin D levels. Alternatively, because BMP7 can induce angiogenesis, 45,46 it is possible variants in BMP7 have a smaller impact on osteonecrosis in older children and adolescents when bony growth is complete and the bony vasculature is already established.…”

Section: Blood 4 February 2016 X Volume 127 Number 5 Genetic Risks mentioning

confidence: 99%

Genetic risk factors for the development of osteonecrosis in children under age 10 treated for acute lymphoblastic leukemia

Karol

Mattano

Yang

et al. 2016

Blood

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• Variants in genes important for mesenchymal stem cell differentiation influence the risk of osteonecrosis in children with ALL under 10 years old.• Variants in genes in the glutamate signaling pathway influence osteonecrosis in children with ALL regardless of age.Osteonecrosis is a dose-limiting toxicity in the treatment of pediatric acute lymphoblastic leukemia (ALL [OR 10.8] in the discovery and replication cohorts, respectively). In a meta-analysis, the BMP7 and PROX1-AS1 variants (rs75161997 and rs1891059, respectively) met the significance threshold of <5 3 10 28. Top replicated SNPs were enriched in enhancers active in mesenchymal stem cells, and analysis of annotated genes demonstrated enrichment in glutamate receptor and adipogenesis pathways. These data may provide new insights into the pathophysiology of osteonecrosis. (Blood. 2016;127(5):558-564)

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Bone Morphogenetic Protein-7 (OP1) and Transforming Growth Factor-β1 Modulate 1,25(OH)2-Vitamin D3-Induced Differentiation of Human Osteoblasts

Cited by 18 publications

References 35 publications

Inhibitory Smads and TGF-β Signaling in Glomerular Cells

Inhibitory Smads and TGF-β Signaling in Glomerular Cells

Platelet-rich plasma and 1,25(OH)2 vitamin D3 synergistically stimulate osteogenic differentiation of adult human mesenchymal stem cells

Genetic risk factors for the development of osteonecrosis in children under age 10 treated for acute lymphoblastic leukemia

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