TY - JOUR
T1 - Folic acid pretreatment and its sustained delivery for chondrogenic differentiation of MSCs
AU - Moon, Yuna
AU - Patel, Madhumita
AU - Um, Soyoun
AU - Lee, Hyun Jung
AU - Park, Sohee
AU - Park, Soo Bong
AU - Cha, Sun Shin
AU - Jeong, Byeongmoon
N1 - Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2022/3
Y1 - 2022/3
N2 - Dietary uptake of folic acid (FA) improves cartilage regeneration. In this work, we discovered that three days of FA treatment is highly effective for promoting chondrogenic differentiation of tonsil-derived mesenchymal stem cells (TMSCs). In a three-dimensional pellet culture, the levels of typical chondrogenic biomarkers, sulfated glycosaminoglycan, proteoglycan, type II collagen (COL II), SRY box transcription factor 9 (SOX 9), cartilage oligomeric matrix protein (COMP), and aggrecan (ACAN) increased significantly in proportion to FA concentration up to 30 μM. At the mRNA expression level, COL II, SOX 9, COMP, and ACAN increased 3.6–6.0-fold with FA treatment at 30 μM compared with the control system that did not receive FA treatment, and the levels with FA treatment were 1.6–2.5 times greater than those in the kartogenin-treated positive control system. FA treatment did not increase type I collagen α1 (COL I α1), an osteogenic biomarker which is a concern with most chondrogenic promoters. At the high FA concentration of 100 μM, significant decreases in chondrogenic biomarkers were observed, which might be related to DNA methylation. A thermogel system incorporating TMSCs and FA provided sustained release of FA over several days, similar to the FA treatment. The thermogel system confirmed the efficacy of FA in promoting chondrogenic promotion of TMSCs. The increased nuclear translocation of core-binding factor β subunit (CBFβ) and the runt-related transcription factor 1 (RUNX1) expression after FA treatment, together with molecular docking studies, suggest that the chondrogenic enhancement mechanism of FA is mediated by CBFβ and RUNX1.
AB - Dietary uptake of folic acid (FA) improves cartilage regeneration. In this work, we discovered that three days of FA treatment is highly effective for promoting chondrogenic differentiation of tonsil-derived mesenchymal stem cells (TMSCs). In a three-dimensional pellet culture, the levels of typical chondrogenic biomarkers, sulfated glycosaminoglycan, proteoglycan, type II collagen (COL II), SRY box transcription factor 9 (SOX 9), cartilage oligomeric matrix protein (COMP), and aggrecan (ACAN) increased significantly in proportion to FA concentration up to 30 μM. At the mRNA expression level, COL II, SOX 9, COMP, and ACAN increased 3.6–6.0-fold with FA treatment at 30 μM compared with the control system that did not receive FA treatment, and the levels with FA treatment were 1.6–2.5 times greater than those in the kartogenin-treated positive control system. FA treatment did not increase type I collagen α1 (COL I α1), an osteogenic biomarker which is a concern with most chondrogenic promoters. At the high FA concentration of 100 μM, significant decreases in chondrogenic biomarkers were observed, which might be related to DNA methylation. A thermogel system incorporating TMSCs and FA provided sustained release of FA over several days, similar to the FA treatment. The thermogel system confirmed the efficacy of FA in promoting chondrogenic promotion of TMSCs. The increased nuclear translocation of core-binding factor β subunit (CBFβ) and the runt-related transcription factor 1 (RUNX1) expression after FA treatment, together with molecular docking studies, suggest that the chondrogenic enhancement mechanism of FA is mediated by CBFβ and RUNX1.
KW - Chondrogenic differentiation
KW - Drug delivery system
KW - Folic acid
KW - In silico model
KW - Mesenchymal stem cell
KW - Thermogel
UR - http://www.scopus.com/inward/record.url?scp=85123696324&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2022.01.018
DO - 10.1016/j.jconrel.2022.01.018
M3 - Article
C2 - 35051494
AN - SCOPUS:85123696324
SN - 0168-3659
VL - 343
SP - 118
EP - 130
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -