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Stimulation of fracture mineralization by salt-inducible kinase inhibitors
- Source :
- Frontiers in Bioengineering and Biotechnology, Vol 12 (2024)
- Publication Year :
- 2024
- Publisher :
- Frontiers Media S.A., 2024.
-
Abstract
- IntroductionOver 6.8 million fractures occur annually in the US, with 10% experiencing delayed- or non-union. Anabolic therapeutics like PTH analogs stimulate fracture repair, and small molecule salt inducible kinase (SIK) inhibitors mimic PTH action. This study tests whether the SIK inhibitor YKL-05-099 accelerates fracture callus osteogenesis.Methods126 female mice underwent femoral shaft pinning and midshaft fracture, receiving daily injections of PBS, YKL-05-099, or PTH. Callus tissues were analyzed via RT-qPCR, histology, single-cell RNA-seq, and μCT imaging. Biomechanical testing evaluated tissue rigidity. A hydrogel-based delivery system for PTH and siRNAs targeting SIK2/SIK3 was developed and tested.ResultsYKL-05-099 and PTH-treated mice showed higher mineralized callus volume fraction and improved structural rigidity. RNA-seq indicated YKL-05-099 increased osteoblast subsets and reduced chondrocyte precursors. Hydrogel-released siRNAs maintained target knockdown, accelerating callus mineralization.DiscussionYKL-05-099 enhances fracture repair, supporting selective SIK inhibitors’ development for clinical use. Hydrogel-based siRNA delivery offers targeted localized treatment at fracture sites.
Details
- Language :
- English
- ISSN :
- 22964185
- Volume :
- 12
- Database :
- Directory of Open Access Journals
- Journal :
- Frontiers in Bioengineering and Biotechnology
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.30c0059e650645d5aab74c54b217fe57
- Document Type :
- article
- Full Text :
- https://doi.org/10.3389/fbioe.2024.1450611