ArticleJCI insight2024
Hedgehog activation promotes osteogenic fates of growth plate resting zone chondrocytes through transient clonal competency.
Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- "Quiescence" in the resting zone of the growth plate: a systematic review.Stem cells (Dayton, Ohio) · 2026Pooled it
- Fracture healing: from molecular and cellular mechanisms to therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Decoding growth hormone actions on human growth plate stem cells.Trends in endocrinology and metabolism: TEM · 2026Article
- Skeletal stem cell lineages in osteosarcoma and bone metastasis.Journal of bone and mineral metabolism · 2026Review
- Bone marrow endosteum houses Hedgehog-susceptible Dlx5-expressing osteoblast precursor cells.Communications biology · 2026Article
- Excess FGFR3 signaling in achondroplasia disrupts turnover of resting zone chondrocytes via CREB signaling.Nature communications · 2026Article
- Effects of nutritional low phosphorus status caused by extremely low phosphorus diet during lactation and early childhood on endochondral ossification in offspring rats.Frontiers in nutrition · 2026Article
- Growth hormone regulates the stem cell population in the growth plate.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Early determination of the dorsal-ventral axis in endochondral ossification in mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025Article
- Growth Plate Skeletal Stem Cells and Their Actions Within the Stem Cell Niche.International journal of molecular sciences · 2025Review
- Challenges of engineering a functional growth plateFrontiers in bioengineering and biotechnology · 2025Review
- The G protein-coupled receptor ADGRG6 maintains mouse growth plate homeostasis through IHH signaling.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024Article
- Endosteal stem cells at the bone-blood interface: A double-edged sword for rapid bone formation: Bone marrow endosteal stem cells provide a robust source of bone-making osteoblasts both in normal and abnormal bone formation.BioEssays : news and reviews in molecular, cellular and developmental biology · 2024Article
- Stimulation of skeletal stem cells in the growth plate promotes linear bone growth.JCI insight · 2024Article
- Periosteum Containing Implicit Stem Cells: A Progressive Source of Inspiration for Bone Tissue Regeneration.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The resting zone of the postnatal growth plate is organized by slow-cycling chondrocytes expressing parathyroid hormone-related protein (PTHrP), which include a subgroup of skeletal stem cells that contribute to the formation of columnar chondrocytes. The PTHrP-Indian hedgehog feedback regulation is essential for sustaining growth plate activities; however, molecular mechanisms regulating cell fates of PTHrP+ resting chondrocytes and their eventual transformation into osteoblasts remain largely undefined. Here, in a mouse model, we specifically activated Hedgehog signaling in PTHrP+ resting chondrocytes and traced the fate of their descendants using a tamoxifen-inducible Pthrp-creER line with patched-1-floxed and tdTomato reporter alleles. Hedgehog-activated PTHrP+ chondrocytes formed large, concentric, clonally expanded cell populations within the resting zone ("patched roses") and generated significantly wider columns of chondrocytes, resulting in hyperplasia of the growth plate. Interestingly, Hedgehog-activated PTHrP+ cell descendants migrated away from the growth plate and transformed into trabecular osteoblasts in the diaphyseal marrow space in the long term. Therefore, Hedgehog activation drives resting zone chondrocytes into transit-amplifying states as proliferating chondrocytes and eventually converts these cells into osteoblasts, unraveling a potentially novel Hedgehog-mediated mechanism that facilitates osteogenic cell fates of PTHrP+ skeletal stem cells.
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Registered trials
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.