ArticleDevelopmental biology2015
Gdf5 progenitors give rise to fibrocartilage cells that mineralize via hedgehog signaling to form the zonal enthesis.
Article in Developmental biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 121 citations in OpenAlex.
- The developing tendon and enthesis are hypoxic and rely on hypoxia-inducible factor 1a during postnatal development.Development (Cambridge, England) · 2026Article
- Multicellular microtissues from fused ligament- and bone-cell spheroids relevant to enthesis repair.Materials today. Bio · 2026Article
- Localized Delivery of a Small Molecule Hedgehog Agonist via Poly(ε-caprolactone) Scaffolds Enhances Tendon-to-Bone Integration.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2026Article
- Advanced engineering strategies for biomaterial scaffolds application in tendon-bone interface regeneration.Burns & trauma · 2026Review
- Low-intensity pulsed ultrasound stimulated hydrogel-polylactic acid composite scaffolds: a dual-cue approach for enhanced rotator cuff healing.Regenerative biomaterials · 2026Article
- The developing tendon and enthesis are hypoxic and rely on hypoxia-inducible factor 1a (bioRxiv : the preprint server for biology · 2025Article
- Internal diseases and molecular mechanisms causing slipped capital femoral epiphysis in children.World journal of orthopedics · 2025Review
- SHED-derived exosome-mimetics promotes rotator cuff tendon-bone healing via macrophage immunomodulation through NF-κB suppression and autophagy activation.Materials today. Bio · 2025Article
- Stem and progenitor cells in the synovial joint as targets for regenerative therapy.Nature reviews. Rheumatology · 2025Review
- Bone marrow adipogenic lineage precursors are the major regulator of bone resorption in adult mice.Bone research · 2025Article
- Hedgehog signaling directs cell differentiation and plays a critical role in tendon enthesis healing.NPJ Regenerative medicine · 2025Article
- Single-cell sequencing reveals cellular heterogeneity and molecular mechanisms in tendon and enthesis injury repair.Frontiers in physiology · 2025Review
- Paracrine signals influence patterns of fibrocartilage differentiation in a lyophilized gelatin hydrogel for applications in rotator cuff repair.Biomaterials science · 2024Article
- Bone marrow adipogenic lineage precursors are the major regulator of bone resorption in adult mice.Research square · 2024Article
- The role of GDF5 in regulating enthesopathy development in the Hyp mouse model of XLH.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024Article
- Interfacial Tissue Regeneration with Bone.Current osteoporosis reports · 2024Review
- Reduction in postnatal weight-bearing does not alter the trajectory of murine meniscus growth and maturation.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2024Article
- Sclerostin modulates mineralization degree and stiffness profile in the fibrocartilaginous enthesis for mechanical tissue integrity.Frontiers in cell and developmental biology · 2024Article
- Article
- Loss of Fgfr1 and Fgfr2 in Scleraxis-lineage cells leads to enlarged bone eminences and attachment cell death.Developmental dynamics : an official publication of the American Association of Anatomists · 2023Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
The sequence of events that leads to the formation of a functionally graded enthesis is not clearly defined. The current study demonstrates that clonal expansion of Gdf5 progenitors contributes to linear growth of the enthesis. Prior to mineralization, Col1+ cells in the enthesis appose Col2+ cells of the underlying primary cartilage. At the onset of enthesis mineralization, cells at the base of the enthesis express alkaline phosphatase, Indian hedgehog, and ColX as they mineralize. The mineralization front then extends towards the tendon midsubstance as cells above the front become encapsulated in mineralized fibrocartilage over time. The hedgehog (Hh) pathway regulates this process, as Hh-responsive Gli1+ cells within the developing enthesis mature from unmineralized to mineralized fibrochondrocytes in response to activated signaling. Hh signaling is required for mineralization, as tissue-specific deletion of its obligate transducer Smoothened in the developing tendon and enthesis cells leads to significant reductions in the apposition of mineralized fibrocartilage. Together, these findings provide a spatiotemporal map of events - from expansion of the embryonic progenitor pool to synthesis of the collagen template and finally mineralization of this template - that leads to the formation of the mature zonal enthesis. These results can inform future tendon-to-bone repair strategies to create a mechanically functional enthesis in which tendon collagen fibers are anchored to bone through mineralized fibrocartilage.
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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.