Up-Regulation of TGF-β Promotes Tendon-to-Bone Healing after Anterior Cruciate Ligament Reconstruction using Bone Marrow-Derived Mesenchymal Stem Cells through the TGF-β/MAPK Signaling Pathway in a New Zealand White Rabbit Model
Background/Aims: This study aimed to explore the role of TGF-β in tendon-to-bone healing after anterior cruciate ligament (ACL) reconstruction using bone marrow-derived mesenchymal stem cells (BMSCs) through the TGF-β/MAPK signaling pathway in a New Zealand white rabbit model. Methods: A total of 72...
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Cell Physiol Biochem Press GmbH & Co KG
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doaj-dfc84e25fa0e4c3482e8ef21a39070eb2020-11-25T00:54:34ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782017-01-0141121322610.1159/000456046456046Up-Regulation of TGF-β Promotes Tendon-to-Bone Healing after Anterior Cruciate Ligament Reconstruction using Bone Marrow-Derived Mesenchymal Stem Cells through the TGF-β/MAPK Signaling Pathway in a New Zealand White Rabbit ModelRui WangBin XuHong-Gang XuBackground/Aims: This study aimed to explore the role of TGF-β in tendon-to-bone healing after anterior cruciate ligament (ACL) reconstruction using bone marrow-derived mesenchymal stem cells (BMSCs) through the TGF-β/MAPK signaling pathway in a New Zealand white rabbit model. Methods: A total of 72 healthy male New Zealand white rabbits were selected for these experiments. Flow cytometry and immunofluorescence were used to detect the expression of BMSC surface markers, and qRT-PCR was performed to detect TGF-β mRNA expression. The ACL reconstruction model was established with autografts. The rabbits were randomly divided into the following groups: inhibition of TGF-β (inhibition), over-expression of TGF-β (over-expression), empty vector and untreated (n = 18 per group). Hematoxylineosin (HE) staining, toluidine blue staining and Masson trichrome staining were conducted to observe any chondrocyte-like cell growth, and biomechanical tests were used to calculate the maximum load and rigidity. Three-dimensional CT imaging and Western blotting were applied to detect changes in bone tunnel size and bone density and the expression levels of TGF-β/MAPK signaling pathway-related proteins, respectively. Results: CD90 and CD44 were positively expressed, while CD11b was not detected. Compared with the empty vector and untreated groups, TGF-β mRNA expression was significantly decreased in the inhibition group but increased in the over-expression group; the latter group had a larger number of fibroblasts, a tighter tendon-bone interface, an increased number of chondrocyte-like cells and fibrochondrocytes, and more collagen fibers than the inhibition, empty vector and untreated groups. Compared with the empty vector and untreated groups, the maximum load and rigidity; the CT values of bone tunnel and bone tunnel margin; and the protein expression levels of TGF-β, p-ERK1/2, p-p38, p-JNK, c-jun and c-myc were significantly down-regulated in the inhibition group but up-regulated in the over-expression group. Conclusion: Our study indicated that up-regulating TGF-β expression in BMSCs from New Zealand white rabbits could promote tendon-to-bone healing after ACL reconstruction by regulating the TGF-β/MAPK signaling pathway.http://www.karger.com/Article/FullText/456046TGF-βTendon-to-bone healingAnterior cruciate ligament reconstructionBone marrow-derived mesenchymal stem cell TGF-β/MAPK signaling pathway |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rui Wang Bin Xu Hong-Gang Xu |
spellingShingle |
Rui Wang Bin Xu Hong-Gang Xu Up-Regulation of TGF-β Promotes Tendon-to-Bone Healing after Anterior Cruciate Ligament Reconstruction using Bone Marrow-Derived Mesenchymal Stem Cells through the TGF-β/MAPK Signaling Pathway in a New Zealand White Rabbit Model Cellular Physiology and Biochemistry TGF-β Tendon-to-bone healing Anterior cruciate ligament reconstruction Bone marrow-derived mesenchymal stem cell TGF-β/MAPK signaling pathway |
author_facet |
Rui Wang Bin Xu Hong-Gang Xu |
author_sort |
Rui Wang |
title |
Up-Regulation of TGF-β Promotes Tendon-to-Bone Healing after Anterior Cruciate Ligament Reconstruction using Bone Marrow-Derived Mesenchymal Stem Cells through the TGF-β/MAPK Signaling Pathway in a New Zealand White Rabbit Model |
title_short |
Up-Regulation of TGF-β Promotes Tendon-to-Bone Healing after Anterior Cruciate Ligament Reconstruction using Bone Marrow-Derived Mesenchymal Stem Cells through the TGF-β/MAPK Signaling Pathway in a New Zealand White Rabbit Model |
title_full |
Up-Regulation of TGF-β Promotes Tendon-to-Bone Healing after Anterior Cruciate Ligament Reconstruction using Bone Marrow-Derived Mesenchymal Stem Cells through the TGF-β/MAPK Signaling Pathway in a New Zealand White Rabbit Model |
title_fullStr |
Up-Regulation of TGF-β Promotes Tendon-to-Bone Healing after Anterior Cruciate Ligament Reconstruction using Bone Marrow-Derived Mesenchymal Stem Cells through the TGF-β/MAPK Signaling Pathway in a New Zealand White Rabbit Model |
title_full_unstemmed |
Up-Regulation of TGF-β Promotes Tendon-to-Bone Healing after Anterior Cruciate Ligament Reconstruction using Bone Marrow-Derived Mesenchymal Stem Cells through the TGF-β/MAPK Signaling Pathway in a New Zealand White Rabbit Model |
title_sort |
up-regulation of tgf-β promotes tendon-to-bone healing after anterior cruciate ligament reconstruction using bone marrow-derived mesenchymal stem cells through the tgf-β/mapk signaling pathway in a new zealand white rabbit model |
publisher |
Cell Physiol Biochem Press GmbH & Co KG |
series |
Cellular Physiology and Biochemistry |
issn |
1015-8987 1421-9778 |
publishDate |
2017-01-01 |
description |
Background/Aims: This study aimed to explore the role of TGF-β in tendon-to-bone healing after anterior cruciate ligament (ACL) reconstruction using bone marrow-derived mesenchymal stem cells (BMSCs) through the TGF-β/MAPK signaling pathway in a New Zealand white rabbit model. Methods: A total of 72 healthy male New Zealand white rabbits were selected for these experiments. Flow cytometry and immunofluorescence were used to detect the expression of BMSC surface markers, and qRT-PCR was performed to detect TGF-β mRNA expression. The ACL reconstruction model was established with autografts. The rabbits were randomly divided into the following groups: inhibition of TGF-β (inhibition), over-expression of TGF-β (over-expression), empty vector and untreated (n = 18 per group). Hematoxylineosin (HE) staining, toluidine blue staining and Masson trichrome staining were conducted to observe any chondrocyte-like cell growth, and biomechanical tests were used to calculate the maximum load and rigidity. Three-dimensional CT imaging and Western blotting were applied to detect changes in bone tunnel size and bone density and the expression levels of TGF-β/MAPK signaling pathway-related proteins, respectively. Results: CD90 and CD44 were positively expressed, while CD11b was not detected. Compared with the empty vector and untreated groups, TGF-β mRNA expression was significantly decreased in the inhibition group but increased in the over-expression group; the latter group had a larger number of fibroblasts, a tighter tendon-bone interface, an increased number of chondrocyte-like cells and fibrochondrocytes, and more collagen fibers than the inhibition, empty vector and untreated groups. Compared with the empty vector and untreated groups, the maximum load and rigidity; the CT values of bone tunnel and bone tunnel margin; and the protein expression levels of TGF-β, p-ERK1/2, p-p38, p-JNK, c-jun and c-myc were significantly down-regulated in the inhibition group but up-regulated in the over-expression group. Conclusion: Our study indicated that up-regulating TGF-β expression in BMSCs from New Zealand white rabbits could promote tendon-to-bone healing after ACL reconstruction by regulating the TGF-β/MAPK signaling pathway. |
topic |
TGF-β Tendon-to-bone healing Anterior cruciate ligament reconstruction Bone marrow-derived mesenchymal stem cell TGF-β/MAPK signaling pathway |
url |
http://www.karger.com/Article/FullText/456046 |
work_keys_str_mv |
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