ArticleThe Journal of biological chemistry2010
Mechano-transduction in osteoblastic cells involves strain-regulated estrogen receptor alpha-mediated control of insulin-like growth factor (IGF) I receptor sensitivity to Ambient IGF, leading to phosphatidylinositol 3-kinase/AKT-dependent Wnt/LRP5 receptor-independent activation of beta-catenin signaling.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 120 citations in OpenAlex.
- Trial
- Sex Hormones & Exercise in the Musculoskeletal System: From Signaling to Structure and Function.Endocrine reviews · 2026Article
- Optimizing Titanium Osseointegration through Thermally Modified Co-Doped Monetite Coatings.ACS biomaterials science & engineering · 2026Article
- Article
- A Review on the Crosstalk between Insulin and Wnt/β-Catenin Signalling for Bone Health.International journal of molecular sciences · 2023Review
- Examining Mechanisms for Voltage-Sensitive Calcium Channel-Mediated Secretion Events in Bone Cells.Calcified tissue international · 2023Review
- Mechanotransduction pathways in articular chondrocytes and the emerging role of estrogen receptor-α.Bone research · 2023Review
- Protein Kinase G2 Is Essential for Skeletal Homeostasis and Adaptation to Mechanical Loading in Male but Not Female Mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023Article
- Mechanosensitive Steroid Hormone Signaling and Cell Fate.Endocrinology · 2022Article
- The osteocyte as a signaling cell.Physiological reviews · 2022Review
- Role of irisin in physiology and pathology.Frontiers in endocrinology · 2022Review
- Article
- Irisin Regulating Skeletal Response to Endurance Exercise in Ovariectomized Mice by Promoting Akt/β-Catenin Pathway.Frontiers in physiology · 2021Article
- Estrogen Receptor α Signaling in Osteoblasts is Required for Mechanotransduction in Bone Fracture Healing.Frontiers in bioengineering and biotechnology · 2021Article
- Insulin growth factor-1 pathway in cervical carcinoma cancer stem cells.Molecular and cellular biochemistry · 2020Article
- Food for Bone: Evidence for a Role for Delta-Tocotrienol in the Physiological Control of Osteoblast Migration.International journal of molecular sciences · 2020Article
- p75NTRCell proliferation · 2020Article
- Potential of delphinidin-3-rutinoside extracted from Solanum melongena L. as promoter of osteoblastic MC3T3-E1 function and antagonist of oxidative damage.European journal of nutrition · 2019Article
- Insulin-like growth factors: actions on the skeleton.Journal of molecular endocrinology · 2018Review
- Role of IGF1 and EFN-EPH signaling in skeletal metabolism.Journal of molecular endocrinology · 2018Review
7 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The capacity of bones to adjust their mass and architecture to withstand the loads of everyday activity derives from the ability of their resident cells to respond appropriately to the strains engendered. To elucidate the mechanisms of strain responsiveness in bone cells, we investigated in vitro the responses of primary mouse osteoblasts and UMR-106 osteoblast-like cells to a single period of dynamic strain. This stimulates a cascade of events, including activation of insulin-like growth factor I receptor (IGF-IR), phosphatidylinositol 3-kinase-mediated phosphorylation of AKT, inhibition of GSK-3beta, increased activation of beta-catenin, and associated lymphoid-enhancing factor/T cell factor-mediated transcription. Initiation of this pathway does not involve the Wnt/LRP5/Frizzled receptor and does not culminate in increased IGF transcription. The effect of strain on IGF-IR is mimicked by exogenous des-(1-3)IGF-I and is blocked by the IGF-IR inhibitor H1356. Inhibition of strain-related prostanoid and nitric oxide production inhibits strain-related (and basal) AKT activity, but their separate ectopic administration does not mimic it. Strain-related IGF-IR activation of AKT requires estrogen receptor alpha (ERalpha) with which IGF-1R physically associates. The ER blocker ICI 182,780 increases the concentration of des-(1-3)IGF-I necessary to activate this cascade, whereas estrogen inhibits both basal AKT activity and its activation by des-(1-3)IGF-I. These data suggest an initial cascade of strain-related events in osteoblasts in which strain activates IGF-IR, in association with ERalpha, so initiating phosphatidylinositol 3-kinase/AKT-dependent activation of beta-catenin and altered lymphoid-enhancing factor/T cell factor transcription. This cascade requires prostanoid/nitric oxide production and is independent of Wnt/LRP5.
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