ArticleNPJ Regenerative medicine2022
A murine model of large-scale bone regeneration reveals a selective requirement for Sonic Hedgehog.
Article in NPJ Regenerative medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Equisetum hyemale enhances local bone regeneration in murine maxillary defects: an in vivo study.Odontology · 2026Article
- Skeletal Maturity and Age-Related Changes in Immune Cells and Circulatory Factors Impair Large-Scale Bone Regeneration.Aging cell · 2025Article
- Current cutting-edge omics techniques on musculoskeletal tissues and diseases.Bone research · 2025Review
- Sonic Hedgehog potentiates BMP9-induced osteogenic differentiation of mesenchymal stem cells.Genes & diseases · 2025Article
- Multi-omics insights into bone tissue injury and healing: bridging orthopedic trauma and regenerative medicine.Burns & trauma · 2025Review
- Mechanistic study of the effect of flexible fixation and load-bearing stress environment on fracture healing and shaping.Animal models and experimental medicine · 2024Article
- Disruption of the creb3l1 gene causes defects in caudal fin regeneration and patterning in zebrafish Danio rerio.Developmental dynamics : an official publication of the American Association of Anatomists · 2024Article
- Acute hyperlipidemia has transient effects on large-scale bone regeneration in male mice.Scientific reports · 2024Article
- Advancing skeletal health and disease research with single-cell RNA sequencing.Military Medical Research · 2024Review
- Sequential application of small molecule therapy enhances chondrogenesis and angiogenesis in murine segmental defect bone repair.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2023Article
- Application of Single-Cell and Spatial Omics in Musculoskeletal Disorder Research.International journal of molecular sciences · 2023Review
- Recent advances in primary cilia in bone metabolism.Frontiers in endocrinology · 2023Review
- The salamander blastema within the broader context of metazoan regeneration.Frontiers in cell and developmental biology · 2023Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Building and maintaining skeletal tissue requires the activity of skeletal stem and progenitor cells (SSPCs). Following injury, local pools of these SSPCs become active and coordinate to build new cartilage and bone tissues. While recent studies have identified specific markers for these SSPCs, how they become activated in different injury contexts is not well-understood. Here, using a model of large-scale rib bone regeneration in mice, we demonstrate that the growth factor, Sonic Hedgehog (SHH), is an early and essential driver of large-scale bone healing. Shh expression is broadly upregulated in the first few days following rib bone resection, and conditional knockout of Shh at early but not late post-injury stages severely inhibits cartilage callus formation and later bone regeneration. Whereas Smoothened (Smo), a key transmembrane component of the Hh pathway, is required in Sox9+ lineage cells for rib regeneration, we find that Shh is required in a Prrx1-expressing, Sox9-negative mesenchymal population. Intriguingly, upregulation of Shh expression and requirements for Shh and Smo may be unique to large-scale injuries, as they are dispensable for both complete rib and femur fracture repair. In addition, single-cell RNA sequencing of callus tissue from animals with deficient Hedgehog signaling reveals a depletion of Cxcl12-expressing cells, which may indicate failed recruitment of Cxcl12-expressing SSPCs during the regenerative response. These results reveal a mechanism by which Shh expression in the local injury environment unleashes large-scale regenerative abilities in the murine rib.
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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.