TY - JOUR
T1 - Intracellular Remodeling and Accumulation of Aberrant Lysosomes in Differentiation of Tonsil-Derived Mesenchymal Stem Cells into Parathyroid-Like Cells
AU - Jo, Young Il
AU - Kim, Gyungah
AU - Jin, Yoon Mi
AU - Park, Yoon Jeong
AU - Kim, Han Su
AU - Park, Yoon Shin
N1 - Funding Information:
This study was supported in part by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning NRF-2013R1A1A3007591 and 2017R1A2B4002611 by the Grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI14C-1557). This work was supported by the research grant of the Chungbuk National University in 2016.
Publisher Copyright:
© 2017, The Korean Tissue Engineering and Regenerative Medicine Society and Springer Science+Business Media Dordrecht.
PY - 2017/8/1
Y1 - 2017/8/1
N2 - Differentiation of mesenchymal stem cells (MSC) into a variety of cell lineages such as adipocytes, osteocytes, and chondrocytes is often accompanied up-regulation of autophagy. In our study, we demonstrated that the expression of autophagy-associated proteins (p-Beclin 1, LC3A, LC3B, p-AMPK, p-mTOR and ATG3, ATG7, and ATG12-5) over a period of time was hardly distinguishable from control tonsil-derived MSC (TMSC). Despite the unnoticeable difference in autophagy activation between differentiated TMSC (dTMSC) and the control (cTMSC), we reported significant changes in intracellular compositions in differentiated TMSC into functional parathyroid-like cells secreting parathyroid hormone (PTH). By using transmission electron microscopy (TEM), we observed accumulation of multivesicular bodies (MVB) comprising small, degraded compartments densely accumulated as dark granular or amorphous clumps, multilamellar bodies and lipid droplets in dTMSC. However, no such structures were found in cTMSC. These results suggest that differentiation of TMSC into parathyroid-like cells producing PTH hormone is hardly dependent on autophagy activation in the beginning of our conditions. Furthermore, our results of intracellular remodeling and accumulated endo-lysosomal storage bodies in the later stages of TMSC differentiation present a possible role of the structures in PTH secretion.
AB - Differentiation of mesenchymal stem cells (MSC) into a variety of cell lineages such as adipocytes, osteocytes, and chondrocytes is often accompanied up-regulation of autophagy. In our study, we demonstrated that the expression of autophagy-associated proteins (p-Beclin 1, LC3A, LC3B, p-AMPK, p-mTOR and ATG3, ATG7, and ATG12-5) over a period of time was hardly distinguishable from control tonsil-derived MSC (TMSC). Despite the unnoticeable difference in autophagy activation between differentiated TMSC (dTMSC) and the control (cTMSC), we reported significant changes in intracellular compositions in differentiated TMSC into functional parathyroid-like cells secreting parathyroid hormone (PTH). By using transmission electron microscopy (TEM), we observed accumulation of multivesicular bodies (MVB) comprising small, degraded compartments densely accumulated as dark granular or amorphous clumps, multilamellar bodies and lipid droplets in dTMSC. However, no such structures were found in cTMSC. These results suggest that differentiation of TMSC into parathyroid-like cells producing PTH hormone is hardly dependent on autophagy activation in the beginning of our conditions. Furthermore, our results of intracellular remodeling and accumulated endo-lysosomal storage bodies in the later stages of TMSC differentiation present a possible role of the structures in PTH secretion.
KW - Autophagy
KW - Multilamellar bodies
KW - Multivesicular bodies
KW - Parathyroid-like differentiation
KW - Tonsil-derived mesenchymal stem cells
UR - http://www.scopus.com/inward/record.url?scp=85026751701&partnerID=8YFLogxK
U2 - 10.1007/s13770-017-0042-5
DO - 10.1007/s13770-017-0042-5
M3 - Article
AN - SCOPUS:85026751701
SN - 1738-2696
VL - 14
SP - 411
EP - 420
JO - Tissue Engineering and Regenerative Medicine
JF - Tissue Engineering and Regenerative Medicine
IS - 4
ER -