ArticleJournal of orthopaedic research : official publication of the Orthopaedic Research Society2021
SM04755, a small-molecule inhibitor of the Wnt pathway, as a potential topical treatment for tendinopathy.
Article in Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 36 citations in OpenAlex.
- A biomimetic hybrid membrane vesicle nanoplatform attenuates tendinopathy through neuroinflammation modulation and tendon regeneration.Cell reports. Medicine · 2026Article
- The use of molecular cues to regenerate musculoskeletal tissues.Innovative surgical sciences · 2026Review
- The current status of various preclinical therapeutic approaches for tendon repair.Annals of medicine · 2024Review
- Why Is Wnt/β-Catenin Not Yet Targeted in Routine Cancer Care?Pharmaceuticals (Basel, Switzerland) · 2024Review
- In silico identification of a novel Cdc2-like kinase 2 (CLK2) inhibitor in triple negative breast cancer.Protein science : a publication of the Protein Society · 2024Article
- 2-Desaza-annomontine (C81) impedes angiogenesis through reduced VEGFR2 expression derived from inhibition of CDC2-like kinases.Angiogenesis · 2024Article
- Pentamidine-loaded gelatin decreases adhesion formation of flexor tendon.Journal of orthopaedic translation · 2024Article
- Cdc2-like kinases: structure, biological function, and therapeutic targets for diseases.Signal transduction and targeted therapy · 2023Review
- Large extracellular vesicles secreted by human iPSC-derived MSCs ameliorate tendinopathyBioactive materials · 2023Article
- [Research advances on the mechanism of Wnt/β-catenin signaling pathway in body surface wound healing].Zhonghua shao shang yu chuang mian xiu fu za zhi · 2023Article
- Molecular mechanisms underlying the action of carcinogens in gastric cancer with a glimpse into targeted therapy.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Advances toward transformative therapies for tendon diseases.Science translational medicine · 2022Review
- Non-Viral Delivery of Gene Therapy to the Tendon.Polymers · 2022Review
- The combination of BMP12 and KY02111 enhances tendon differentiation in bone marrow-derived equine mesenchymal stromal cells (BM-eMSCs).Journal of equine science · 2022Article
- Cross-Talk between Wnt Signaling and Src Tyrosine Kinase.Biomedicines · 2022Review
- SM04755, a small-molecule inhibitor of the Wnt pathway, as a potential topical treatment for tendinopathy.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2021Article
- Dual-Specificity, Tyrosine Phosphorylation-Regulated Kinases (DYRKs) and cdc2-Like Kinases (CLKs) in Human Disease, an Overview.International journal of molecular sciences · 2021Review
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Wnt pathway is upregulated in tendinopathy, affecting inflammation and tenocyte differentiation. Given its potential role in tendinopathy, this signaling pathway may be a relevant target for treatment. The current study examined the therapeutic potential of SM04755, a topical, small-molecule Wnt pathway inhibitor, for the treatment of tendinopathy using in vitro assays and animal models. In vitro, SM04755 decreased Wnt pathway activity, induced tenocyte differentiation, and inhibited catabolic enzymes and pro-inflammatory cytokines in human mesenchymal stem cells, rat tendon-derived stem cells, and human peripheral blood mononuclear cells. Evaluation of the mechanism of action of SM04755 by biochemical profiling and computational modeling identified CDC-like kinase 2 (CLK2) and dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) as molecular targets. CLK and DYRK1A inhibition by siRNA knockdown or pharmacological inhibition induced tenocyte differentiation and reduced tenocyte catabolism. In vivo, topically applied SM04755 showed therapeutically relevant exposure in tendons with low systemic exposure and no detectable toxicity in rats. Moreover, SM04755 showed reduced tendon inflammation and evidence of tendon regeneration, decreased pain, and improved weight-bearing function in rat collagenase-induced tendinopathy models compared with vehicle control. Together, these data demonstrate that CLK2 and DYRK1A inhibition by SM04755 resulted in Wnt pathway inhibition, enhanced tenocyte differentiation and protection, and reduced inflammation. SM04755 has the potential to benefit symptoms and modify disease processes in tendinopathy.
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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 Socratic graph.