ArticleOsteoarthritis and cartilage2023
Targeting the hedgehog signaling pathway to improve tendon-to-bone integration.
Article in Osteoarthritis and cartilage, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 8 citations in OpenAlex.
- 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
- Tendon Dysfunction in Collagen VI-Related Myopathies: Novel Mechanistic Insights with Therapeutic Potential.International journal of molecular sciences · 2025Review
- [Effect of stretch on taurine upregulated gene 1-mediated miR-545-3p/cannbinoida receptor 2 pathway regulating distraction osteogenesis in rats].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2025Article
- Achieving tendon enthesis regeneration across length scales.Current opinion in biomedical engineering · 2024Article
- KIAA0753 enhances osteoblast differentiation suppressed by diabetes.Journal of cellular and molecular medicine · 2024Article
- Interfacial Tissue Regeneration with Bone.Current osteoporosis reports · 2024Review
- Preclinical tendon and ligament models: Beyond the 3Rs (replacement, reduction, and refinement) to 5W1H (why, who, what, where, when, how).Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2023Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 2 countries.
Funding
Abstract
objectiveWhile the role of hedgehog (Hh) signaling in promoting zonal fibrocartilage production during development is well-established, whether this pathway can be leveraged to improve tendon-to-bone repair in adults is unknown. Our objective was to genetically and pharmacologically stimulate the Hh pathway in cells that give rise to zonal fibrocartilaginous attachments to promote tendon-to-bone integration.
designHh signaling was stimulated genetically via constitutive Smo (SmoM2 construct) activation of bone marrow stromal cells or pharmacologically via systemic agonist delivery to mice following anterior cruciate ligament reconstruction (ACLR). To assess tunnel integration, we measured mineralized fibrocartilage (MFC) formation in these mice 28 days post-surgery and performed tunnel pullout testing.
resultsHh pathway-related genes increased in cells forming the zonal attachments in wild-type mice. Both genetic and pharmacologic stimulation of the Hh pathway increased MFC formation and integration strength 28 days post-surgery. We next conducted studies to define the role of Hh in specific stages of the tunnel integration process. We found Hh agonist treatment increased the proliferation of the progenitor pool in the first week post-surgery. Additionally, genetic stimulation led to continued MFC production in the later stages of the integration process. These results indicate that Hh signaling plays an important biphasic role in cell proliferation and differentiation towards fibrochondrocytes following ACLR.
conclusionThis study reveals a biphasic role for Hh signaling during the tendon-to-bone integration process after ACLR. In addition, the Hh pathway is a promising therapeutic target to improve tendon-to-bone repair outcomes.
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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.