TY - JOUR
T1 - Aging-affected msc functions and severity of periodontal tissue destruction in a ligature-induced mouse periodontitis model
AU - Aung, Kyaw Thu
AU - Akiyama, Kentaro
AU - Kunitomo, Masayoshi
AU - Mun, Aung Ye
AU - Tosa, Ikue
AU - Nguyen, Ha Thi Thu
AU - Zhang, Jiewen
AU - Kohno, Teisaku
AU - Ono, Mitsuaki
AU - Hara, Emilio Satoshi
AU - Kuboki, Takuo
N1 - Funding Information:
Acknowledgments: This research was funded by JSPS KAKENHI Grant Number JP20K21679, JP20K23109.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - Mesenchymal stem cells (MSCs) are known to play important roles in the repair of lost or damaged tissues and immunotolerance. On the other hand, aging is known to impair MSC function. However, little is currently known about how aged MSCs affect the host response to the local inflammatory condition and tissue deterioration in periodontitis, which is a progressive destructive disease of the periodontal tissue potentially leading to multiple tooth loss. In this study, we examined the relationship between aging-induced impairment of MSC function and the severity of periodontal tissue destruction associated with the decrease in host immunomodulatory response using a ligature-induced periodontitis model in young and aged mice. The results of micro computerized tomography (micro-CT) and histological analysis revealed a more severe bone loss associated with increased osteoclast activity in aged (50-week-old) mice compared to young (5-week-old) mice. Immunostaining analysis revealed that, in aged mice, the accumulation of inflammatory T and B cells was higher, whereas the percentage of platelet-derived growth factor receptor α (PDGFRα)+ MSCs, which are known to modulate the apoptosis of T cells, was significantly lower than in young mice. In vitro analysis of MSC function showed that the expression of surface antigen markers for MSCs (Sca-1, CD90, CD146), colony formation, migration, and osteogenic differentiation of aged MSCs were significantly declined compared to those of young MSCs. Moreover, a significantly higher proportion of aged MSCs were positive for the senescence-associated β galactosidase activity. Importantly, aged MSCs presented a decreased expression of FAS-L, which was associated with a lower immunomodulatory property of aged MSCs to induce T cell apoptosis in co-cultures compared with young MSCs. In summary, this is the first study showing that aging-induced impairment of MSC function, including immunomodulatory response, is potentially correlated with progressive periodontal tissue deterioration.
AB - Mesenchymal stem cells (MSCs) are known to play important roles in the repair of lost or damaged tissues and immunotolerance. On the other hand, aging is known to impair MSC function. However, little is currently known about how aged MSCs affect the host response to the local inflammatory condition and tissue deterioration in periodontitis, which is a progressive destructive disease of the periodontal tissue potentially leading to multiple tooth loss. In this study, we examined the relationship between aging-induced impairment of MSC function and the severity of periodontal tissue destruction associated with the decrease in host immunomodulatory response using a ligature-induced periodontitis model in young and aged mice. The results of micro computerized tomography (micro-CT) and histological analysis revealed a more severe bone loss associated with increased osteoclast activity in aged (50-week-old) mice compared to young (5-week-old) mice. Immunostaining analysis revealed that, in aged mice, the accumulation of inflammatory T and B cells was higher, whereas the percentage of platelet-derived growth factor receptor α (PDGFRα)+ MSCs, which are known to modulate the apoptosis of T cells, was significantly lower than in young mice. In vitro analysis of MSC function showed that the expression of surface antigen markers for MSCs (Sca-1, CD90, CD146), colony formation, migration, and osteogenic differentiation of aged MSCs were significantly declined compared to those of young MSCs. Moreover, a significantly higher proportion of aged MSCs were positive for the senescence-associated β galactosidase activity. Importantly, aged MSCs presented a decreased expression of FAS-L, which was associated with a lower immunomodulatory property of aged MSCs to induce T cell apoptosis in co-cultures compared with young MSCs. In summary, this is the first study showing that aging-induced impairment of MSC function, including immunomodulatory response, is potentially correlated with progressive periodontal tissue deterioration.
KW - Aging
KW - Bone resorption
KW - Immunomodulation
KW - Mesenchymal stem cell
KW - Periodontitis
KW - Tissue destruction
UR - http://www.scopus.com/inward/record.url?scp=85095609015&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85095609015&partnerID=8YFLogxK
U2 - 10.3390/ijms21218103
DO - 10.3390/ijms21218103
M3 - Article
C2 - 33143068
AN - SCOPUS:85095609015
SN - 1661-6596
VL - 21
SP - 1
EP - 20
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 21
M1 - 8103
ER -