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Therapeutic Potential of Tauroursodeoxycholic Acid for the Treatment of Osteoporosis

Tauroursodeoxycholic acid (TUDCA) is a US FDA-approved hydrophilic bile acid for the treatment of chronic cholestatic liver disease. In the present study, we investigate the effects of TUDCA on the proliferation and differentiation of osteoblasts and its therapeutic effect on a mice model of osteopo...

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Autores principales: Ahn, Tae-Keun, Kim, Kyoung-Tae, Joshi, Hari Prasad, Park, Kwang Hwan, Kyung, Jae Won, Choi, Un-Yong, Sohn, Seil, Sheen, Seung-Hun, Shin, Dong-Eun, Lee, Soo-Hong, Han, In-Bo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349164/
https://www.ncbi.nlm.nih.gov/pubmed/32560070
http://dx.doi.org/10.3390/ijms21124274
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author Ahn, Tae-Keun
Kim, Kyoung-Tae
Joshi, Hari Prasad
Park, Kwang Hwan
Kyung, Jae Won
Choi, Un-Yong
Sohn, Seil
Sheen, Seung-Hun
Shin, Dong-Eun
Lee, Soo-Hong
Han, In-Bo
author_facet Ahn, Tae-Keun
Kim, Kyoung-Tae
Joshi, Hari Prasad
Park, Kwang Hwan
Kyung, Jae Won
Choi, Un-Yong
Sohn, Seil
Sheen, Seung-Hun
Shin, Dong-Eun
Lee, Soo-Hong
Han, In-Bo
author_sort Ahn, Tae-Keun
collection PubMed
description Tauroursodeoxycholic acid (TUDCA) is a US FDA-approved hydrophilic bile acid for the treatment of chronic cholestatic liver disease. In the present study, we investigate the effects of TUDCA on the proliferation and differentiation of osteoblasts and its therapeutic effect on a mice model of osteoporosis. Following treatment with different concentrations of TUDCA, cell viability, differentiation, and mineralization were measured. Three-month-old female C57BL/6 mice were randomly divided into three groups (n = 8 mice per group): (i) normal mice as the control group, (ii) ovariectomy (OVX) group (receiving phosphate-buffered saline (PBS) treatment every other day for 4 weeks), and (iii) OVX group with TUDCA (receiving TUDCA treatment every other day for 4 weeks starting 6 weeks after OVX). At 11 weeks post-surgery, serum levels of procollagen type I N-terminal propeptides (PINP) and type I collagen crosslinked C-telopeptides (CTX) were measured, and all mice were sacrificed to examine the distal femur by micro-computed tomography (CT) scans and histology. TUDCA (100 nM, 1 µM) significantly increased the proliferation and viability of osteoblasts and osteoblast differentiation and mineralization when used in vitro. Furthermore, TUDCA neutralized the detrimental effects of methylprednisolone (methylprednisolone-induced osteoblast apoptosis). In the TUDCA treatment group the PINP level was higher and the CTX level was lower, but these levels were not significantly different compared to the PBS treatment group. Micro-CT and histology showed that the TUDCA treatment group preserved more trabecular structures in the distal femur compared to the PBS treatment group. In addition, the TUDCA treatment group increased the percentage bone volume with respect to the total bone volume, bone mineral density, and mice distal femur trabeculae compared with the PBS treatment group. Taken together, our findings suggest that TUDCA may provide a favorable effect on bones and could be used for the prevention and treatment of osteoporosis.
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spelling pubmed-73491642020-07-22 Therapeutic Potential of Tauroursodeoxycholic Acid for the Treatment of Osteoporosis Ahn, Tae-Keun Kim, Kyoung-Tae Joshi, Hari Prasad Park, Kwang Hwan Kyung, Jae Won Choi, Un-Yong Sohn, Seil Sheen, Seung-Hun Shin, Dong-Eun Lee, Soo-Hong Han, In-Bo Int J Mol Sci Article Tauroursodeoxycholic acid (TUDCA) is a US FDA-approved hydrophilic bile acid for the treatment of chronic cholestatic liver disease. In the present study, we investigate the effects of TUDCA on the proliferation and differentiation of osteoblasts and its therapeutic effect on a mice model of osteoporosis. Following treatment with different concentrations of TUDCA, cell viability, differentiation, and mineralization were measured. Three-month-old female C57BL/6 mice were randomly divided into three groups (n = 8 mice per group): (i) normal mice as the control group, (ii) ovariectomy (OVX) group (receiving phosphate-buffered saline (PBS) treatment every other day for 4 weeks), and (iii) OVX group with TUDCA (receiving TUDCA treatment every other day for 4 weeks starting 6 weeks after OVX). At 11 weeks post-surgery, serum levels of procollagen type I N-terminal propeptides (PINP) and type I collagen crosslinked C-telopeptides (CTX) were measured, and all mice were sacrificed to examine the distal femur by micro-computed tomography (CT) scans and histology. TUDCA (100 nM, 1 µM) significantly increased the proliferation and viability of osteoblasts and osteoblast differentiation and mineralization when used in vitro. Furthermore, TUDCA neutralized the detrimental effects of methylprednisolone (methylprednisolone-induced osteoblast apoptosis). In the TUDCA treatment group the PINP level was higher and the CTX level was lower, but these levels were not significantly different compared to the PBS treatment group. Micro-CT and histology showed that the TUDCA treatment group preserved more trabecular structures in the distal femur compared to the PBS treatment group. In addition, the TUDCA treatment group increased the percentage bone volume with respect to the total bone volume, bone mineral density, and mice distal femur trabeculae compared with the PBS treatment group. Taken together, our findings suggest that TUDCA may provide a favorable effect on bones and could be used for the prevention and treatment of osteoporosis. MDPI 2020-06-16 /pmc/articles/PMC7349164/ /pubmed/32560070 http://dx.doi.org/10.3390/ijms21124274 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ahn, Tae-Keun
Kim, Kyoung-Tae
Joshi, Hari Prasad
Park, Kwang Hwan
Kyung, Jae Won
Choi, Un-Yong
Sohn, Seil
Sheen, Seung-Hun
Shin, Dong-Eun
Lee, Soo-Hong
Han, In-Bo
Therapeutic Potential of Tauroursodeoxycholic Acid for the Treatment of Osteoporosis
title Therapeutic Potential of Tauroursodeoxycholic Acid for the Treatment of Osteoporosis
title_full Therapeutic Potential of Tauroursodeoxycholic Acid for the Treatment of Osteoporosis
title_fullStr Therapeutic Potential of Tauroursodeoxycholic Acid for the Treatment of Osteoporosis
title_full_unstemmed Therapeutic Potential of Tauroursodeoxycholic Acid for the Treatment of Osteoporosis
title_short Therapeutic Potential of Tauroursodeoxycholic Acid for the Treatment of Osteoporosis
title_sort therapeutic potential of tauroursodeoxycholic acid for the treatment of osteoporosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349164/
https://www.ncbi.nlm.nih.gov/pubmed/32560070
http://dx.doi.org/10.3390/ijms21124274
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