Administration of tauroursodeoxycholic acid enhances osteogenic differentiation of bone marrow-derived mesenchymal stem cells and bone regeneration.
It is known that osteogenic differentiation of mesenchymal stem cells (MSCs) can be promoted by suppression of adipogenesis of MSCs. We have recently found that the chemical chaperone tauroursodeoxycholic acid (TUDCA) significantly reduces adipogenesis of MSCs. In the present study, we examined whether TUDCA can promote osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMMSCs) by regulating Integrin 5 (ITGA5) associated with activation of ERK1/2 signal pathway and thereby enhance bone tissue regeneration by reducing apoptosis and the inflammatory response. TUDCA treatment promoted in vitro osteogenic differentiation of BMMSCs and in vivo bone tissue regeneration in a calvarial defect model, as confirmed by micro-computed tomography, histological staining, and immunohistochemistry for osteocalcin. In addition, TUDCA treatment significantly decreased apoptosis and the inflammatory response in vivo and in vitro, which is important to enhance bone tissue regeneration. These results indicate that TUDCA plays a critical role in enhancing osteogenesis of BMMSCs, and is therefore a potential alternative drug for bone tissue regeneration.
Department of Biomedical Science, College of Life Science, CHA University, Seongnam-si, Republic of Korea.
Byung-Hyun
BH
Cha
Interdisciplinary Program for Bioengineering, Seoul National University, Seoul 151-744, Republic of Korea.
Moon-Joo
MJ
Jung
Department of Biomedical Science, College of Life Science, CHA University, Seongnam-si, Republic of Korea.
Bo-Kyung
BK
Moon
Department of Biomedical Science, College of Life Science, CHA University, Seongnam-si, Republic of Korea.
Jin-Su
JS
Kim
Interdisciplinary Program for Bioengineering, Seoul National University, Seoul 151-744, Republic of Korea.
Yoonji
Y
Ma
Department of Biomedical Science, College of Life Science, CHA University, Seongnam-si, Republic of Korea.
Yoshie
Y
Arai
Interdisciplinary Program for Bioengineering, Seoul National University, Seoul 151-744, Republic of Korea.
Myungkyung
M
Noh
Interdisciplinary Program for Bioengineering, Seoul National University, Seoul 151-744, Republic of Korea.
Jung-Youn
JY
Shin
Interdisciplinary Program for Bioengineering, Seoul National University, Seoul 151-744, Republic of Korea; School of Chemical and Biological Engineering, Seoul National University, Seoul 151-744, Republic of Korea; Bio-MAX Institute, Institute for Chemical Processes, Seoul National University, Seoul 151-744, Republic of Korea. Electronic address: byungskim@snu.ac.kr.
Byung-Soo
BS
Kim
Department of Biomedical Science, College of Life Science, CHA University, Seongnam-si, Republic of Korea. Electronic address: soohong@cha.ac.kr.
Soo-Hong
SH
Lee
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology*; D001861:Bone Regeneration / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D007249:Inflammation / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008807:Mice, Inbred BALB C; D010012:Osteogenesis / Q000187:drug effects*; D012886:Skull / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D013655:Taurochenodeoxycholic Acid / Q000008:administration & dosage* / Q000494:pharmacology*; D055114:X-Ray Microtomography
D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine
Apoptosis; Bone tissue regeneration; Inflammatory; Mesenchymal stem cells; Osteogenic differentiation; Tauroursodeoxycholic acid