Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Salicylate Can Enhance Osteogenic Differentiation of Human Periosteum-derived Mesenchymal Stem Cells

Salicylate가 성체줄기세포의 골분화에 미치는 영향

  • Kim, Bo Gyu (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University) ;
  • Lee, A ram (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University) ;
  • Lee, Bo Young (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University) ;
  • Shim, Sungbo (Department of Biochemistry, Chungbuk National University) ;
  • Moon, Dong kyu (Department of Orthopedic Surgery and Institute of Health Sciences, School of Medicine and Hospital, Gyeongsang National University) ;
  • Hwang, Sun-Chul (Department of Orthopedic Surgery and Institute of Health Sciences, School of Medicine and Hospital, Gyeongsang National University) ;
  • Byun, June-Ho (Department of Oral and Maxillofacial Surgery and Institute of Health Sciences, School of Medicine and Hospital, Gyeongsang National University) ;
  • Woo, Dong Kyun (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University)
  • Received : 2018.10.10
  • Accepted : 2018.10.22
  • Published : 2018.12.30
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Abstract

Due to a rapidly expanding aging population, the incidence of degenerative bone disease has increased, and efforts to handle the issue using regenerative medicine have become more important. In order to control various bone diseases such as osteoarthritis and osteoporosis, regenerative medicine utilizing adult stem cells has been extensively studied. And it is now clear that the mitochondrial energy metabolism, oxidative phosphorylation, is important for the process of stem cell differentiation. Interestingly, a recent study reported that salicylate promotes mitochondrial biogenesis by regulating the expression of $PGC-1{\alpha}$ in murine cells. However, the possible effects of salicylate on osteogenic differentiation through increased mitochondrial biogenesis in stem cells remain unknown. Thus, here we investigated whether salicylate could influence osteogenic differentiation and mitochondrial biogenesis of periosteum-derived mesenchymal stem cells (POMSCs). We found that salicylate treatments of POMSCs undergoing osteogenic differentiation increased the activity of alkaline phosphatase, a well-known early marker of bone cell differentiation. In addition, we observed that mitochondrial mass was increased by salicylate treatments in POMSCs. Together, these results indicate that salicylate can enhance osteogenic differentiation and mitochondrial biogenesis in POMSCs. Therefore, the findings in this study suggest that small molecules augmenting mitochondrial function such as salicylate can be a novel modulator for osteogenic differentiation and regenerative medicine.

최근 들어 급속한 고령화 사회가 진행되고 있으며 이로 인해 골관절염과 골다공증 등의 퇴행성 골질환 환자수도 동반하여 증가하고 있다. 따라서 고령화에 따른 골관련 질환의 새로운 제어와 치료법 개발을 위해 성체줄기세포의 골세포 분화유도를 활용한 재생의학도 활발히 연구되고 있다. 또한 관련 연구에서 줄기세포의 분화과정에서 미토콘드리아의 산화적인산화가 중요하다고 알려지고 있다. 흥미롭게도 최근 연구에서 아스피린의 주성분인 salicylate가 동물세포의 미토콘드리아 생합성을 증진시키는 효과가 보고되었다. 그러나 성체줄기세포에서 salicylate가 골세포분화나 미토콘드리아 생합성을 유도할 수 있는지에 대한 연구결과는 미비한 실정이다. 본 연구에서는 인체 골막 유래의 성체줄기세포를 이용하여 골세포분화나 미토콘드리아 생합성에 대한 salicylate의 영향을 분석하였다. 골막 유래 성체줄기세포의 골세포 분화유도 과정에 동반한 salicylate 처리는 잘 알려진 골세포분화 표지자인 alkaline phosphatase의 활성을 증가시키는 결과를 본 연구에서 얻었다. 이러한 연구결과는 salicylate가 줄기세포로부터 골세포로의 분화를 조절할 수 있는 물질이 될 수 있음을 제시한다. 또한 이러한 골세포 분화과정에서 미토콘드리아 생합성도 salicylate 처리에 의해 증가됨이 관찰되었다. 따라서, 미토콘드리아 생합성이나 기능을 조절하는 물질이 성체줄기세포의 골세포 분화과정에도 영향을 줄 수 있으며, 이러한 물질이 골세포분화나 재생의학의 새로운 조절 물질로 응용될 수 있음을 제시한다.

Keywords

SMGHBM_2018_v28n12_1455_f0001.png 이미지

Fig. 1. Effects of salicylate on the proliferation and viability of POMSCs.

SMGHBM_2018_v28n12_1455_f0002.png 이미지

Fig. 2. Effects of salicylate on osteogenic differentiation of POMSCs.

SMGHBM_2018_v28n12_1455_f0003.png 이미지

Fig. 3. Effects of salicylate on mitochondrial biogenesis during osteogenic differentiation of POMSCs.

SMGHBM_2018_v28n12_1455_f0004.png 이미지

Fig. 4. Visualization and quantitation of mitochondrial biogenesis during osteogenic differentiation of POMSCs.

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