ArticleThe Journal of biological chemistry2012
Gli1 protein participates in Hedgehog-mediated specification of osteoblast lineage during endochondral ossification.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 91 citations in OpenAlex.
- Sonic Hedgehog potentiates BMP9-induced osteogenic differentiation of mesenchymal stem cells.Genes & diseases · 2025Article
- Serinc5 Regulates Sequential Chondrocyte Differentiation by Inhibiting Sox9 Function in Pre-Hypertrophic Chondrocytes.Journal of cellular physiology · 2025Article
- CRP inhibits the osteoblastic differentiation of OPCs via the up-regulation of primary cilia and repression of the Hedgehog signaling pathway.Medical oncology (Northwood, London, England) · 2024Article
- Linoleic acid blunts early osteoblast differentiation and impairs oxidative phosphorylation in vitro.Prostaglandins, leukotrienes, and essential fatty acids · 2024Article
- Hedgehog activation promotes osteogenic fates of growth plate resting zone chondrocytes through transient clonal competency.JCI insight · 2024Article
- Application of dental pulp stem cells for bone regeneration.Frontiers in medicine · 2024Review
- The Role of Gli1Biomolecules · 2023Review
- A New Strategy for the Old Challenge of Thalidomide: Systems Biology Prioritization of Potential Immunomodulatory Drug (IMiD)-Targeted Transcription Factors.International journal of molecular sciences · 2023Article
- Bone Sialoprotein Is Critical for Alveolar Bone Healing in Mice.Journal of dental research · 2023Article
- Runx2 regulates chromatin accessibility to direct the osteoblast program at neonatal stages.Cell reports · 2022Article
- Exogenous Indian hedgehog antagonist damages intervertebral discs homeostasis in adult mice.Journal of orthopaedic translation · 2022Article
- On the horizon: Hedgehog signaling to heal broken bones.Bone research · 2022Review
- The long and winding road: homeostatic and disordered haematopoietic microenvironmental niches: a narrative review.Biomaterials translational · 2022Review
- In Vitro Osteoinductivity Assay of Hydroxylapatite Scaffolds, Obtained with Biomorphic Transformation Processes, Assessed Using Human Adipose Stem Cell Cultures.International journal of molecular sciences · 2021Article
- CRISPR editing of the GLI1 first intron abrogates GLI1 expression and differentially alters lineage commitment.Stem cells (Dayton, Ohio) · 2021Article
- Mechanisms of bone development and repair.Nature reviews. Molecular cell biology · 2020Review
- TGF-β/Smad2 signalling regulates enchondral bone formation of Gli1Cell proliferation · 2020Article
- Hedgehog Signaling in Skeletal Development: Roles of Indian Hedgehog and the Mode of Its Action.International journal of molecular sciences · 2020Review
- Article
- Growth Plate Chondrocytes: Skeletal Development, Growth and Beyond.International journal of molecular sciences · 2019Review
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
With regard to Hedgehog signaling in mammalian development, the majority of research has focused on Gli2 and Gli3 rather than Gli1. This is because Gli1(-/-) mice do not show any gross abnormalities in adulthood, and no detailed analyses of fetal Gli1(-/-) mice are available. In this study, we investigated the physiological role of Gli1 in osteogenesis. Histological analyses revealed that bone formation was impaired in Gli1(-/-) fetuses compared with WT fetuses. Gli1(-/-) perichondrial cells expressed neither runt-related transcription factor 2 (Runx2) nor osterix, master regulators of osteogenesis, in contrast to WT cells. In vitro analyses showed that overexpression of Gli1 up-regulated early osteogenesis-related genes in both WT and Runx2(-/-) perichondrial cells, and Gli1 activated transcription of those genes via its association with their 5'-regulatory regions, underlying the function of Gli1 in the perichondrium. Moreover, Gli1(-/-);Gli2(-/-) mice showed more severe phenotypes of impaired bone formation than either Gli1(-/-) or Gli2(-/-) mice, and osteoblast differentiation was impaired in Gli1(-/-);Gli3(-/-) perichondrial cells compared with Gli3(-/-) cells in vitro. These data suggest that Gli1 itself can induce early osteoblast differentiation, at least to some extent, in a Runx2-independent manner. It also plays a redundant role with Gli2 and is involved in the repressor function of Gli3 in osteogenesis. On the basis of these findings, we propose that upon Hedgehog input, Gli1 functions collectively with Gli2 and Gli3 in osteogenesis.
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