期刊
DEVELOPMENT
卷 149, 期 5, 页码 -出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.199995
关键词
Bone; Osteoblasts; Notch signaling; Fracture healing; Regeneration; Zebrafish
资金
- Orthopaedic Research Society Collaborative Exchange Grant
- National Institutes of Health [F32 DE026346, R01 AR069700, R35 DE027550, R01 DK074482, R01 DE030660, R01 AR066028]
- U.S. Department of Defense Congressionally Directed Medical Research Programs [W81XWH-15-1-0689]
This study shows that Notch signaling is induced during the early stages of bone healing and its modulation can affect the size and quality of bone regeneration. The findings suggest that targeting Notch signaling may provide a new strategy to enhance bone healing in mammals.
Loss or damage to the mandible caused by trauma, treatment of oral malignancies, and other diseases is treated using bonegrafting techniques that suffer from numerous shortcomings and contraindications. Zebrafish naturally heal large injuries to mandibular bone, offering an opportunity to understand how to boost intrinsic healing potential. Using a novel her6:mCherry Notch reporter, we show that canonical Notch signaling is induced during the initial stages of cartilage callus formation in both mesenchymal cells and chondrocytes following surgical mandibulectomy. We also show that modulation of Notch signaling during the initial post-operative period results in lasting changes to regenerate bone quantity one month later. Pharmacological inhibition of Notch signaling reduces the size of the cartilage callus and delays its conversion into bone. resulting in non-union. Conversely, conditional transgenic activation of Notch signaling accelerates conversion of the cartilage callus into bone. improving bone healing. Given the conserved functions of this pathway in bone repair across vertebrates, we propose that targeted activation of Notch signaling during the early phases of bone healing in mammals may both augment the size of the initial callus and boost its ossification into reparative bone.
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