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

Stem Cells Int

Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Shanghai Stomatological Hospital and School of Stomatology, Fudan University, Shanghai, China.

Published: December 2024

AI Article Synopsis

  • Dental pulp stem cells (DPSCs) show promise for muscle injury repair, but their ability to differentiate into muscle cells is currently limited.
  • Treating DPSCs with Noggin, which inhibits bone morphogenetic protein (BMP) signals, enhances myogenic differentiation, increases myogenic markers, and generates satellite-like cells, improving muscle regeneration.
  • Implanting Noggin-treated DPSCs in a mouse model of muscle loss resulted in significant reductions in defect size and scar tissue, indicating that BMP/Smad signaling regulation by Noggin effectively promotes muscle repair.

Article Abstract

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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699990PMC
http://dx.doi.org/10.1155/sci/2812390DOI Listing

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

Stem Cells Int

December 2024

Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Shanghai Stomatological Hospital and School of Stomatology, Fudan University, Shanghai, China.

Article Synopsis
  • Dental pulp stem cells (DPSCs) show promise for muscle injury repair, but their ability to differentiate into muscle cells is currently limited.
  • Treating DPSCs with Noggin, which inhibits bone morphogenetic protein (BMP) signals, enhances myogenic differentiation, increases myogenic markers, and generates satellite-like cells, improving muscle regeneration.
  • Implanting Noggin-treated DPSCs in a mouse model of muscle loss resulted in significant reductions in defect size and scar tissue, indicating that BMP/Smad signaling regulation by Noggin effectively promotes muscle repair.
View Article and Find Full Text PDF

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