ArticleJournal of orthopaedic research : official publication of the Orthopaedic Research Society2019
Activation of hedgehog signaling by systemic agonist improves fracture healing in aged mice.
Article in Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
23 citing papers in PubMed, 40 citations in OpenAlex.
- Chondrocytes in fracture healing: A review of chondrocyte journey.Chinese medical journal · 2026Review
- Hedgehog signaling pathway is an influential factor on vascular biology: a review.Journal of physiology and biochemistry · 2025Review
- Research advances of nanomaterials for the acceleration of fracture healing.Bioactive materials · 2024Review
- Hedgehog Activation for Enhanced Rotator Cuff Tendon-to-Bone Healing.The American journal of sports medicine · 2023Article
- Targeting the hedgehog signaling pathway to improve tendon-to-bone integration.Osteoarthritis and cartilage · 2023Article
- 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
- Primary cilia support cartilage regeneration after injury.International journal of oral science · 2023Article
- Bifidobacterium longum supplementation improves age-related delays in fracture repair.Aging cell · 2023Article
- The role of hypertrophic chondrocytes in regulation of the cartilage-to-bone transition in fracture healing.Bone reports · 2022Article
- Understanding Abnormal SMO-SHH Signaling in Autism Spectrum Disorder: Potential Drug Target and Therapeutic Goals.Cellular and molecular neurobiology · 2022Review
- On the horizon: Hedgehog signaling to heal broken bones.Bone research · 2022Review
- Cryogel Scaffold-Mediated Delivery of Adipose-Derived Stem Cells Promotes Healing in Murine Model of Atrophic Non-Union.Frontiers in bioengineering and biotechnology · 2022Article
- Postnatal Osterix but not DMP1 lineage cells significantly contribute to intramembranous ossification in three preclinical models of bone injury.Frontiers in physiology · 2022Article
- Hedgehog signaling underlying tendon and enthesis development and pathology.Matrix biology : journal of the International Society for Matrix Biology · 2022Review
- Ablation of Proliferating Osteoblast Lineage Cells After Fracture Leads to Atrophic Nonunion in a Mouse Model.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2021Article
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- Activation of Cilia-Independent Hedgehog/GLI1 Signaling as a Novel Concept for Neuroblastoma Therapy.Cancers · 2021Article
- Article
- Exogenous PTH 1-34 Attenuates Impaired Fracture Healing in Endogenous PTH Deficiency Mice via Activating Indian Hedgehog Signaling Pathway and Accelerating Endochondral Ossification.Frontiers in cell and developmental biology · 2021Article
- Inspired by nature: facile design of nanoclay-organic hydrogel bone sealant with multifunctional properties for robust bone regeneration.Advanced functional materials · 2020Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Fracture healing is a complex process of many coordinated biological pathways. This system can go awry resulting in nonunion, which leads to significant patient morbidity. The Hedgehog (Hh) signaling pathway is upregulated in fracture healing. We hypothesized that the Hh signaling pathway can be pharmacologically modulated to positively affect fracture healing. Diaphyseal femur fractures were created in elderly mice (18 months, C57BL/6 females), which have a blunted and delayed healing response compared to younger mice, and were stabilized with intramedullary pins. To activate the Hh pathway we targeted the receptor Smoothened using an agonist (Hh-Ag1.5 [Hh-Ag]) and compared this to a vehicle control. Expression of Hh target genes were significantly increased in the fracture callus of the agonist group compared to controls, indicating pathway activation. Expression of osteogenic and chondrogenic-related genes was greatly upregulated in fracture callus versus intact femora, although Hh agonist treatment did not consistently enhance this response. Blindly graded, radiographic callus healing scores were significantly higher in the Hh-Ag groups at post operative day (POD) 14, indicating earlier callus bridging. On microCT, Hh-Ag treatment led to greater callus volume (+40%) and bone volume (+25%) at POD21. By day 14, callus vascularity, as assessed by 3D microCT angiography vessel volume, was 85% greater in the Hh-Ag group. Finally, mechanical strength of the calluses in the Hh-Ag groups was significantly greater than in the control groups at POD21. In conclusion, systemic administration of a Hh agonist appears to improve the osseous and vascular healing responses in a mouse fracture healing-impaired model. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.
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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.