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Effects of Deferoxamine on Inflammation and Osteoclastogenesis: in vitro and in vivo model

Other Titles
 데페록사민이 염증과 파골 세포 형성에 미치는 영향: in vitro 및 in vivo 모델 
Authors
 이고은 
College
 College of Dentistry (치과대학) 
Department
 Dept. of Pediatric Dentistry (소아치과학교실) 
Degree
박사
Issue Date
2021-08
Abstract
Replacement and inflammatory resorption are serious complications associated with delayed replantation of avulsed teeth. This study aimed to assess whether deferoxamine (DFO) can suppress inflammation and osteoclastogenesis in vitro and attenuate inflammation and bone resorption in replanted rat tooth model. Cell viability and lipopolysaccharide (LPS)-induced inflammation were evaluated in RAW264.7 cells. Receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis was confirmed using tartrate-resistant acid phosphatase staining, measurement of the levels of reactive oxygen species (ROS) and quantitative reverse transcriptase-polymerase chain reaction. RANKL-treated cells were exposed to different concentrations of DFO and hypoxia-related gene expression was confirmed by quantitative real-time polymerase chain reaction. The maxillary left molars of 31 six-week-old male Sprague Dawley rats were extracted and stored in saline (n = 10) or DFO solution (n = 21) before replantation. Micro-computed tomography (micro-CT) imaging and histological analysis were performed to evaluate inflammation and root and alveolar bone resorption. Results showed that DFO treatment led to a significant attenuation of the release of nitric oxide (p < 0.01) and expression of pro-inflammatory (p < 0.05) and osteoclastogenic genes (p < 0.01). DFO also reduced ROS production, mitochondrial biogenesis related gene encoding CAMP responsive element binding protein 1 / gene encoding PPARG coactivator 1 beta mechanism and stimulated nuclear factor erythroid 2-related factor 2 / heme oxygenase 1 signaling pathway. In addition, the expression of hypoxia-related genes increased. Furthermore, results from micro-CT and histological analysis provided evidence regarding decrease in inflammation and hard tissue resorption in the DFO group. Overall, these results suggest that DFO reduces inflammation and osteoclastogenesis in a tooth replantation model, and thus needs to be further investigated as a root surface treatment option for an avulsed tooth.

탈구된 치아의 재식이 지연되는 경우 대치 및 염증성 흡수와 같은 심각한 합병증이 발병한다. 본 연구의 목적은 데페록사민이 in vitro에서 염증 및 파골세포의 형성을 억제하고, 쥐의 치아의 재식실험에서 염증과 골 흡수에 미치는 영향을 평가하기 위함이다. 본 연구는 in vitro 실험에서 세포 생존율과 지질 다당류에 의한 염증 여부를 평가하였다. RANKL이 유도하는 파골 세포 형성 은 tartrate-resistant acid phosphatase 염색법, 활성산소종의 농도 측정 및 실시간 중합효소 연쇄반응분석을 통해 분석하였다. In vivo 실험은 Sprague Dawley 수컷 31마리의 대구치를 발치하여 식염수 또는 데페록사민에 각각 5분 담근 후 재식하였다. 마이크로 컴퓨터 단층 촬영 영상과 조직학적 분석을 시행하여 염증과 치근 및 골흡수를 평가하였다. 데페록사민을 처리한 결과 in vitro에서는 염증과 골분화가 현저하게 감소하는 것을 확인하였다. 또한 활성산소종의 발현 및 CAMP responsive element binding protein 1 / gene encoding PPARG coactivator 1 beta 신호 과정을 억제하였으며, nuclear factor erythroid 2-related factor 와 heme oxygenase 1 신호전달체계를 활성화시키는 것으로 나타났다. 그밖에 저산소증 관련 유전자의 발현이 증가하였다. In vivo 실험에 대한 방사선 및 조직학적 분석 결과 염증 및 경조직의 흡수가 감소하는 경향을 보였다. 이러한 결과는 데페록사민이 탈구된 치아 재식모델에서 염증과 파골 세포 형성을 감소시킴을 시사하며, 향후 탈구된 치아의 치근 표면 처리제로써 좋은 후보군이 될 수 있음을 나타낸다.
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Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Pediatric Dentistry (소아치과학교실) > 3. Dissertation
Yonsei Authors
Lee, Koeun(이고은)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/185603
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