Noggin Combined With Human Dental Pulp Stem Cells to Promote Skeletal Muscle Regeneration

A proper source of stem cells is key to muscle injury repair. Dental pulp stem cells (DPSCs) are an ideal source for the treatment of muscle injuries due to their high proliferative and differentiation capacities. However, the current myogenic induction efficiency of human DPSCs hinders their use in...

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Main Authors: Meng-Han Zhang, Li-Ming Yu, Wei-Hua Zhang, Jia-Jia Deng, Bing-Jing Sun, Mei-Hua Chen, Wei Huang, Jiao Li, Hua He, Xin-Xin Han, Yue-Hua Liu
Format: Article
Language:English
Published: Wiley 2024-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/sci/2812390
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author Meng-Han Zhang
Li-Ming Yu
Wei-Hua Zhang
Jia-Jia Deng
Bing-Jing Sun
Mei-Hua Chen
Wei Huang
Jiao Li
Hua He
Xin-Xin Han
Yue-Hua Liu
author_facet Meng-Han Zhang
Li-Ming Yu
Wei-Hua Zhang
Jia-Jia Deng
Bing-Jing Sun
Mei-Hua Chen
Wei Huang
Jiao Li
Hua He
Xin-Xin Han
Yue-Hua Liu
author_sort Meng-Han Zhang
collection DOAJ
description A proper source of stem cells is key to muscle injury repair. Dental pulp stem cells (DPSCs) are an ideal source for the treatment of muscle injuries due to their high proliferative and differentiation capacities. However, the current myogenic induction efficiency of human DPSCs hinders their use in muscle regeneration due to the unknown induction mechanism. In this study, we treated human DPSCs with Noggin, a secreted antagonist of bone morphogenetic protein (BMP), and discovered that Noggin can effectively promote myotube formation. We also found that Noggin can accelerate the skeletal myogenic differentiation (MyoD) of DPSCs and promote the generation of Pax7+ satellite-like cells. Noggin increased the expression of myogenic markers and the transcriptional and translational abundance of satellite cell (SC) markers in DPSCs. Moreover, BMP4 inhibited Pax7 expression and activated p-Smad1/5/9, while Noggin eliminated BMP4-induced p-Smad1/5/9 in DPSCs. This finding suggests that Noggin antagonizes BMP by downregulating p-Smad and facilitates the MyoD of DPSCs. Then, we implanted Noggin-pretreated DPSCs combined with Matrigel into the mouse tibialis anterior muscle with volumetric muscle loss (VML) and observed a 73% reduction in the size of the defect and a 69% decrease in scar tissue. Noggin-treated DPSCs can benefit the Pax7+ SC pool and promote muscle regeneration. This work reveals that Noggin can enhance the production of satellite-like cells from the MyoD of DPSCs by regulating BMP/Smad signaling, and these satellite-like cell bioconstructs might possess a relatively fast capacity for muscle regeneration.
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spelling doaj-art-7e80171f4dcc4c9aaa68b52f502e8e272025-01-05T00:00:04ZengWileyStem Cells International1687-96782024-01-01202410.1155/sci/2812390Noggin Combined With Human Dental Pulp Stem Cells to Promote Skeletal Muscle RegenerationMeng-Han Zhang0Li-Ming Yu1Wei-Hua Zhang2Jia-Jia Deng3Bing-Jing Sun4Mei-Hua Chen5Wei Huang6Jiao Li7Hua He8Xin-Xin Han9Yue-Hua Liu10Shanghai Key Laboratory of Craniomaxillofacial Development and DiseasesShanghai Key Laboratory of Craniomaxillofacial Development and DiseasesShanghai Key Laboratory of Craniomaxillofacial Development and DiseasesShanghai Key Laboratory of Craniomaxillofacial Development and DiseasesShanghai Key Laboratory of Craniomaxillofacial Development and DiseasesShanghai Key Laboratory of Craniomaxillofacial Development and DiseasesShanghai Key Laboratory of Craniomaxillofacial Development and DiseasesShanghai Key Laboratory of Craniomaxillofacial Development and DiseasesDepartment of NeurosurgeryShanghai Key Laboratory of Craniomaxillofacial Development and DiseasesShanghai Key Laboratory of Craniomaxillofacial Development and DiseasesA proper source of stem cells is key to muscle injury repair. Dental pulp stem cells (DPSCs) are an ideal source for the treatment of muscle injuries due to their high proliferative and differentiation capacities. However, the current myogenic induction efficiency of human DPSCs hinders their use in muscle regeneration due to the unknown induction mechanism. In this study, we treated human DPSCs with Noggin, a secreted antagonist of bone morphogenetic protein (BMP), and discovered that Noggin can effectively promote myotube formation. We also found that Noggin can accelerate the skeletal myogenic differentiation (MyoD) of DPSCs and promote the generation of Pax7+ satellite-like cells. Noggin increased the expression of myogenic markers and the transcriptional and translational abundance of satellite cell (SC) markers in DPSCs. Moreover, BMP4 inhibited Pax7 expression and activated p-Smad1/5/9, while Noggin eliminated BMP4-induced p-Smad1/5/9 in DPSCs. This finding suggests that Noggin antagonizes BMP by downregulating p-Smad and facilitates the MyoD of DPSCs. Then, we implanted Noggin-pretreated DPSCs combined with Matrigel into the mouse tibialis anterior muscle with volumetric muscle loss (VML) and observed a 73% reduction in the size of the defect and a 69% decrease in scar tissue. Noggin-treated DPSCs can benefit the Pax7+ SC pool and promote muscle regeneration. This work reveals that Noggin can enhance the production of satellite-like cells from the MyoD of DPSCs by regulating BMP/Smad signaling, and these satellite-like cell bioconstructs might possess a relatively fast capacity for muscle regeneration.http://dx.doi.org/10.1155/sci/2812390
spellingShingle Meng-Han Zhang
Li-Ming Yu
Wei-Hua Zhang
Jia-Jia Deng
Bing-Jing Sun
Mei-Hua Chen
Wei Huang
Jiao Li
Hua He
Xin-Xin Han
Yue-Hua Liu
Noggin Combined With Human Dental Pulp Stem Cells to Promote Skeletal Muscle Regeneration
Stem Cells International
title Noggin Combined With Human Dental Pulp Stem Cells to Promote Skeletal Muscle Regeneration
title_full Noggin Combined With Human Dental Pulp Stem Cells to Promote Skeletal Muscle Regeneration
title_fullStr Noggin Combined With Human Dental Pulp Stem Cells to Promote Skeletal Muscle Regeneration
title_full_unstemmed Noggin Combined With Human Dental Pulp Stem Cells to Promote Skeletal Muscle Regeneration
title_short Noggin Combined With Human Dental Pulp Stem Cells to Promote Skeletal Muscle Regeneration
title_sort noggin combined with human dental pulp stem cells to promote skeletal muscle regeneration
url http://dx.doi.org/10.1155/sci/2812390
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