ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2013
The regulation of runt-related transcription factor 2 by fibroblast growth factor-2 and connexin43 requires the inositol polyphosphate/protein kinase Cδ cascade.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 45 citations in OpenAlex.
- Review
- Pannexins in the musculoskeletal system: new targets for development and disease progression.Bone research · 2024Review
- Connexin43 in Musculoskeletal System: New Targets for Development and Disease Progression.Aging and disease · 2022Article
- Bone fracture healing: perspectives according to molecular basis.Journal of bone and mineral metabolism · 2021Review
- Lineage-specific differentiation of osteogenic progenitors from pluripotent stem cells reveals the FGF1-RUNX2 association in neural crest-derived osteoprogenitors.Stem cells (Dayton, Ohio) · 2020Article
- Article
- Connexin43 regulates osteoprotegerin expression via ERK1/2 -dependent recruitment of Sp1.Biochemical and biophysical research communications · 2019Article
- Molecular signaling in bone cells: Regulation of cell differentiation and survival.Advances in protein chemistry and structural biology · 2019Review
- Diminished Canonical β-Catenin Signaling During Osteoblast Differentiation Contributes to Osteopenia in Progeria.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2018Article
- Microtubules tune mechanotransduction through NOX2 and TRPV4 to decrease sclerostin abundance in osteocytes.Science signaling · 2017Article
- microRNA Regulation of Skeletal Development.Current osteoporosis reports · 2017Review
- Connexin43 and Runx2 Interact to Affect Cortical Bone Geometry, Skeletal Development, and Osteoblast and Osteoclast Function.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2017Article
- Connexin43 and the Intercellular Signaling Network Regulating Skeletal Remodeling.Current osteoporosis reports · 2017Review
- Defective signaling, osteoblastogenesis and bone remodeling in a mouse model of connexin 43 C-terminal truncation.Journal of cell science · 2017Article
- All-trans retinoic acid shifts rosiglitazone-induced adipogenic differentiation to osteogenic differentiation in mouse embryonic fibroblasts.International journal of molecular medicine · 2016Article
- Deficiency of the intermediate filament synemin reduces bone mass in vivo.American journal of physiology. Cell physiology · 2016Article
- Inhibition of connexin 43 prevents trauma-induced heterotopic ossification.Scientific reports · 2016Article
- Communication of cAMP by connexin43 gap junctions regulates osteoblast signaling and gene expression.Cellular signalling · 2016Article
- Genetic insights into the mechanisms of Fgf signaling.Genes & development · 2016Review
- Connexins in the skeleton.Seminars in cell & developmental biology · 2016Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Connexin43 (Cx43) plays a critical role in osteoblast function and bone mass accrual, yet the identity of the second messengers communicated by Cx43 gap junctions, the targets of these second messengers and how they regulate osteoblast function remain largely unknown. We have shown that alterations of Cx43 expression in osteoblasts can impact the responsiveness to fibroblast growth factor-2 (FGF2), by modulating the transcriptional activity of runt-related transcription factor 2 (Runx2). In this study, we examined the contribution of the phospholipase Cγ1/inositol polyphosphate/protein kinase C delta (PKCδ) cascade to the Cx43-dependent transcriptional response of MC3T3 osteoblasts to FGF2. Knockdown of expression and/or inhibition of function of phospholipase Cγ1, inositol polyphosphate multikinase, which generates inositol 1,3,4,5-tetrakisphosphate (InsP₄) and InsP₅, and inositol hexakisphosphate kinase 1/2, which generates inositol pyrophosphates, prevented the ability of Cx43 to potentiate FGF2-induced signaling through Runx2. Conversely, overexpression of phospholipase Cγ1 and inositol hexakisphosphate kinase 1/2 enhanced FGF2 activation of Runx2 and the effect of Cx43 overexpression on this response. Disruption of these pathways blocked the nuclear accumulation of PKCδ and the FGF2-dependent interaction of PKCδ and Runx2, reducing Runx2 transcriptional activity. These data reveal that FGF2-signaling involves the inositol polyphosphate cascade, including inositol hexakisphosphate kinase (IP6K), and demonstrate that IP6K regulates Runx2 and osteoblast gene expression. Additionally, these data implicate the water-soluble inositol polyphosphates as mediators of the Cx43-dependent amplification of the osteoblast response to FGF2, and suggest that these low molecular weight second messengers may be biologically relevant mediators of osteoblast function that are communicated by Cx43-gap junctions.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.