Effect of NF-κB Haploinsufficiency on Calvarial Bone Healing Public Deposited

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  • Effect of NF-[kappa]B Haploinsufficiency on Calvarial Bone Healing
Last Modified
  • June 7, 2019
Creator
  • Liang, Ruiwei
    • Affiliation: School of Dentistry, Oral and Craniofacial Biomedicine PhD Program
Abstract
  • Bone defect is a major and challenging health concern. The treatment for bone defect aims to enhance bone regeneration, which is highly regulated by many molecular signaling pathways. Growing evidence suggested that proper inflammatory signaling was crucial for bone regeneration. Previous study showed that treatment of MSCs with expression of NF-κB increased MSCs engraftment in damaged tissue. Previous work in our lab indicated a role of NF-κB on osteoblast differentiation during physiological bone development. The present study was designed to study role of NF-κB signaling in bone healing using genetically-modified mouse with haploinsufficiency of p65 in osteoblasts. Here, we showed that mice with osteoprogenitor-specific NF-κB haploinsufficiency displayed reduced calvarial defect bone repair manifested by micro-CT and histological analysis. The progenitor cells from p65 haploinsufficient mice demonstrated fewer CFU-OB colonies and decreased osteoblastic markers expression (Sp7, Alp and Bsp) in response to rhBMP2. Furthermore, rhBMP2 mediated Smad phosphorylation was disrupted in the absence of sufficient p65 signal. Therefore, we concluded that NF-κB haploinsufficiency impairs bone repair by downregulation of BMP2 mediated canonical Smads signaling and osteogenic differentiation. The effect of inflammatory mediators on bone formation was complex and yet to be elucidated. Based on our findings, we proposed a direct regulatory role of NF-κB in rhBMP2 mediated bone repair, suggesting that sufficient inflammatory cues are essential for bone regeneration. Uncovering the function of NF-κB in MSC-mediated repair will improve understanding of bone regeneration mechanism and provide a clue for bone regenerative therapy for treatment of bony defect.
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  • In Copyright
Advisor
  • Ko, Ching-Chang
  • Webster-Cyriaque, Jennifer
  • Everett, Eric
  • Cooper, Lyndon F.
  • Zadeh, Homa
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2015
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  • Chapel Hill, NC
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