ArticleThe Journal of biological chemistry2013
Hedgehog-Gli activators direct osteo-chondrogenic function of bone morphogenetic protein toward osteogenesis in the perichondrium.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 63 citations in OpenAlex.
- Mechanical Stimulation Drives Multicellular Synergy and Signaling Pathways in Developing Skeletal Tissues.Sports medicine (Auckland, N.Z.) · 2026Review
- A Modular Bioinstructive Platform Reveals Mechanistic Insights into Additive-Free, Topography-Driven Osteogenesis.Advanced healthcare materials · 2026Article
- Growth Plate Skeletal Stem Cells and Their Actions Within the Stem Cell Niche.International journal of molecular sciences · 2025Review
- Hedgehog Signalling in Osteogenesis and Bone Metabolism: Molecular Mechanisms, Regulatory Networks and Implications for Skeletal Disease.Journal of cellular and molecular medicine · 2025Review
- A Hedgehog-Foxf axis coordinates dental follicle-derived alveolar bone formation.Nature communications · 2025Article
- Challenges of engineering a functional growth plateFrontiers in bioengineering and biotechnology · 2025Review
- Hedgehog activation promotes osteogenic fates of growth plate resting zone chondrocytes through transient clonal competency.JCI insight · 2024Article
- Wnt signaling: Essential roles in osteoblast differentiation, bone metabolism and therapeutic implications for bone and skeletal disorders.Genes & diseases · 2023Review
- Hypomorphic and dominant-negative impact of truncated SOX9 dysregulates Hedgehog-Wnt signaling, causing campomelia.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Caspase-9 inhibition decreases expression of Mmp9 during chondrogenesis.Histochemistry and cell biology · 2022Article
- Targeting extracellular matrix stiffness and mechanotransducers to improve cancer therapy.Journal of hematology & oncology · 2022Review
- Evolutionary rewiring of regulatory networks contributes to phenotypic differences between human and mouse orthologous genes.Nucleic acids research · 2022Article
- Molecular Mechanisms of Chondrocyte Proliferation and Differentiation.Frontiers in cell and developmental biology · 2021Review
- Mechanisms of bone development and repair.Nature reviews. Molecular cell biology · 2020Review
- Hedgehog Signaling in Skeletal Development: Roles of Indian Hedgehog and the Mode of Its Action.International journal of molecular sciences · 2020Review
- Review
- Review
- Growth Plate Chondrocytes: Skeletal Development, Growth and Beyond.International journal of molecular sciences · 2019Review
- Mechanisms of synovial joint and articular cartilage development.Cellular and molecular life sciences : CMLS · 2019Review
- Regulation of Hedgehog signaling Offers A Novel Perspective for Bone Homeostasis Disorder Treatment.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Specification of progenitors into the osteoblast lineage is an essential event for skeletogenesis. During endochondral ossification, cells in the perichondrium give rise to osteoblast precursors. Hedgehog (Hh) and bone morphogenetic protein (BMP) are suggested to regulate the commitment of these cells. However, properties of perichondrial cells and regulatory mechanisms of the specification process are still poorly understood. Here, we investigated the machineries by combining a novel organ culture system and single-cell expression analysis with mouse genetics and biochemical analyses. In a metatarsal organ culture reproducing bone collar formation, activation of BMP signaling enhanced the bone collar formation cooperatively with Hh input, whereas the signaling induced ectopic chondrocyte formation in the perichondrium without Hh input. Similar phenotypes were also observed in compound mutant mice, where signaling activities of Hh and BMP were genetically manipulated. Single-cell quantitative RT-PCR analyses showed heterogeneity of perichondrial cells in terms of natural characteristics and responsiveness to Hh input. In vitro analyses revealed that Hh signaling suppressed BMP-induced chondrogenic differentiation; Gli1 inhibited the expression of Sox5, Sox6, and Sox9 (SRY box-containing gene 9) as well as transactivation by Sox9. Indeed, ectopic expression of chondrocyte maker genes were observed in the perichondrium of metatarsals in Gli1(-/-) fetuses, and the phenotype was more severe in Gli1(-/-);Gli2(-/-) newborns. These data suggest that Hh-Gli activators alter the function of BMP to specify perichondrial cells into osteoblasts; the timing of Hh input and its target populations are critical for BMP function.
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