Prolyl Isomerase Pin1-mediated Conformational Change and Subnuclear Focal Accumulation of Runx2 Are Crucial for Fibroblast Growth Factor 2 (FGF2)-induced Osteoblast Differentiation

Yoon, Won‐Joon; Cho, Young‐Dan; Kim, Woo Jin; Bae, Hyun Cheol; Islam, Rabia; Woo, Kyung Mi; Baek, Jeong‐Hwa; Bae, Suk‐Chul; Ryoo, Hyun‐Mo

doi:10.1074/jbc.m113.516237

Cited by 41 publications

(74 citation statements)

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“…In differentiated osteoblasts, Wnt3a prevents apoptosis through ␤-catenin-dependent signaling cascades involving Src/ERK and PI3K/AKT (45), and the TGF␤ and Notch signaling pathways also maintain cross-talk with the Wnt signaling pathway (46 -49). Pin1 target sequences are shared by several protein kinases, such as ERK, cyclin-dependent kinase, and GSK3a (26). Therefore, we suggest that the conformational change of each of the three different phosphorylation sites probably has different biological implications.…”

Section: Discussionmentioning

confidence: 86%

“…Ds-Red Pin1 WT and mutant constructs have also been described previously (26). Full-length ␤-catenin cDNAs were generated by PCR and subcloned between BamH1 and Not1 sites in pcDNA3.1, respectively, to create FLAG epitope fusion proteins.…”

Section: Methodsmentioning

confidence: 99%

“…Pin1-catalyzed, post-phosphorylation conformational regulation often functions as a molecular timer (24). We have found previously that the interaction of Pin1 with Runx2, the major transcription factor for osteoblast differentiation, is critical for bone development (25,26). We showed that Pin1 hetero and KO mice exhibit reduced mineralization at birth.…”

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confidence: 90%

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Pin1-mediated Modification Prolongs the Nuclear Retention of β-Catenin in Wnt3a-induced Osteoblast Differentiation

Shin¹,

Islam²,

Yoon³

et al. 2016

Journal of Biological Chemistry

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The canonical Wnt signaling pathway, in which ␤-catenin nuclear localization is a crucial step, plays an important role in osteoblast differentiation. Pin1, a prolyl isomerase, is also known as a key enzyme in osteogenesis. However, the role of Pin1 in canonical Wnt signal-induced osteoblast differentiation is poorly understood. We found that Pin1 deficiency caused osteopenia and reduction of ␤-catenin in bone lining cells. Similarly, Pin1 knockdown or treatment with Pin1 inhibitors strongly decreased the nuclear ␤-catenin level, TOP flash activity, and expression of bone marker genes induced by canonical Wnt activation and vice versa in Pin1 overexpression. Pin1 interacts directly with and isomerizes ␤-catenin in the nucleus. The isomerized ␤-catenin could not bind to nuclear adenomatous polyposis coli, which drives ␤-catenin out of the nucleus for proteasomal degradation, which consequently increases the retention of ␤-catenin in the nucleus and might explain the decrease of ␤-catenin ubiquitination. These results indicate that Pin1 could be a critical target to modulate ␤-catenin-mediated osteogenesis.

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Section: Discussionmentioning

confidence: 86%

Section: Methodsmentioning

confidence: 99%

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Pin1-mediated Modification Prolongs the Nuclear Retention of β-Catenin in Wnt3a-induced Osteoblast Differentiation

Shin¹,

Islam²,

Yoon³

et al. 2016

Journal of Biological Chemistry

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“…In early osteoblast precursor cells, activation of ERK1/2 by FGFR signaling primarily leads to increased cell proliferation (Choi et al 2008;Miraoui et al 2009). In more mature cells, ERK1/2 activation by FGF2 enhances acetylation and stabilization of RUNX2, a key transcription factor involved in osteoblastogenesis and bone formation (Xiao et al 2002;Park et al 2010;Yoon et al 2014). ERK1/2 signaling is also involved in Runx2 expression and osteoblast differentiation induced by FGF18-mediated activation of FGFR1/FGFR2 in murine osteoblast precursor cells (Hamidouche et al 2010).…”

Section: Intramembranous Mesenchymal Condensationsmentioning

confidence: 99%

Fibroblast growth factor signaling in skeletal development and disease

2015

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Fibroblast growth factor (FGF) signaling pathways are essential regulators of vertebrate skeletal development. FGF signaling regulates development of the limb bud and formation of the mesenchymal condensation and has key roles in regulating chondrogenesis, osteogenesis, and bone and mineral homeostasis. This review updates our review on FGFs in skeletal development published in Genes & Development in 2002, examines progress made on understanding the functions of the FGF signaling pathway during critical stages of skeletogenesis, and explores the mechanisms by which mutations in FGF signaling molecules cause skeletal malformations in humans. Links between FGF signaling pathways and other interacting pathways that are critical for skeletal development and could be exploited to treat genetic diseases and repair bone are also explored.

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“…Amongst the factors activating osteoblastogenesis are the WNT/β-catenin pathway and Msx2, Runx2 and osterix transcription factors' expression, whereas peroxisome proliferator-activated receptors γ (PPARγ) and members of the C/EBP family (CCAAT-enhancer binding protein) promote adipogenesis [6][7][8]. The PPARγ nuclear hormone receptor subfamily is de facto a group of transcription factors activated by ligands that also includes steroid hormone, vitamin D and retinoid acid receptors.…”

Section: Adipocytes and Osteoblastogenesismentioning

confidence: 99%

Bone and adipose tissue – more and more interdependence

Dytfeld¹

2014

Reumatologia

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Słowa kluczowe: osteoporoza, adipokiny, osteokalcyna. S t r e s z c z e n i eWspólnym prekursorem osteoblastów i adipocytów w szpiku kostnym są mezenchymalne komórki progenitorowe. Wpływ różnora-kich czynników warunkuje ich różnicowanie się w kierunku jednej z tych linii, co może mieć znaczenie dla późniejszych zmian patologicznych układu kostnego. Liczne dowody z badań eksperymentalnych i klinicznych przemawiają także za wzajemnymi wielorakimi zależnościami między szkieletem a tkanką tłuszczową. Liczne produkty adipocytów -leptyna, adiponektyna i inne -w sposób pośredni lub bezpośredni wpływają na zachodzące nieustannie procesy kościotworzenia i resorpcji kostnej. Wiedza na ich temat weryfikuje nasze poglądy na temat otyłości, osteoporozy i złamań niskoenergetycznych. Wiadomo także, że remodeling kostny, proces wymagający energii, jest w dużym stopniu zależny od insuliny, a tkanka kostna wytwarza osteokalcynę -hormon, którego rola daleko wykracza poza wyznaczanie ram obrotu kostnego. Coraz więcej faktów przemawia za endokrynną funkcją szkieletu. S u m m a r yIn bone marrow, osteoblasts and adipocytes originate from common progenitor cells -mesenchymal stem cells (MSCs). The further cell differentiation towards one of the two lines, depending on numerous factors, might have an impact on pathologies of bone in further life. Evidence from experimental and clinical studies indicates multiple reciprocal links between skeleton and adipose tissue. Numerous adipocyte products -leptin, adiponectin, etc. -directly or indirectly affect bone formation and resorption, which take place constantly. This knowledge verifies our views on obesity, osteoporosis and fragility fractures. We also know that bone remodeling, a process that requires energy, is heavily dependent on insulin; moreover, bone is a source of osteocalcin, a hormone whose role goes far beyond determining the level of bone turnover. The endocrine role of the skeleton becomes a reality.

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Prolyl Isomerase Pin1-mediated Conformational Change and Subnuclear Focal Accumulation of Runx2 Are Crucial for Fibroblast Growth Factor 2 (FGF2)-induced Osteoblast Differentiation

Cited by 41 publications

References 54 publications

Pin1-mediated Modification Prolongs the Nuclear Retention of β-Catenin in Wnt3a-induced Osteoblast Differentiation

Pin1-mediated Modification Prolongs the Nuclear Retention of β-Catenin in Wnt3a-induced Osteoblast Differentiation

Fibroblast growth factor signaling in skeletal development and disease

Bone and adipose tissue – more and more interdependence

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