Nicotinamide riboside enhances chondrogenic differentiation of human adipose stem cells via inducing SIRT1-mediated deacetylation of SMAD7 and activation of TGF-β/SMAD2/3 pathway
- 1Department of Plastic and Reconstructive Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853 China
- 2Senior Department of Burns and Plastic Surgery, The Fourth Medical Center of Chinese PLA General Hospital, Beijing, 100048 China
Abstract
Mesenchymal stem cells (MSCs) are widely regarded as a promising candidate for cartilage regeneration, and MSC-based therapies have demonstrated therapeutic potential in promoting cartilage repair. Nevertheless, the chondrogenic differentiation efficacy still requires further improvement. This study identified that Nicotinamide Riboside, a precursor of nicotinamide adenine dinucleotide (NAD⁺), significantly enhances chondrogenic differentiation efficiency of human adipose-derived stem cells (hADSCs), primary by activating the TGF-β/SMAD2/3 signaling pathway. Mechanistically, we demonstrated that NR upregulated the expression of SIRT1 and enhanced SIRT1 activity during the induction of chondrogenesis, thereby promoting the deacetylation and subsequent degradation of SMAD7. NR-mediated reduction of SMAD7 results in enhanced phosphorylation of SMAD2/3 and activation of the TGF-β/SMAD2/3 signaling pathway. SIRT1-mediated deacetylation of SMAD7 is a key factor in NR-enhanced chondrogenic differentiation, as disruption of the interaction between SIRT1 and SMAD7 significantly abolishes the promotive effect of NR on chondrogenesis. Collectively, our study demonstrates that NR enhanced chondrogenic differentiation of hADSCs by regulating SIRT1-mediated deacetylation of SMAD7 and activation of TGF-β/SMAD2/3 pathway. NR may therefore possess prospects as a promising supplement for MSC-based cartilage regeneration and repair therapies.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13287-026-05226-8.
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BibTeX
@article{xu2026nicotinamide,
title = {{Nicotinamide riboside enhances chondrogenic differentiation of human adipose stem cells via inducing SIRT1-mediated deacetylation of SMAD7 and activation of TGF-β/SMAD2/3 pathway}},
author = {Yichi Xu and Jun Shu and Youbai Chen and Haimiao Wang and Ruoxu Zhang and Muzi Chen and Ran Tao},
journal = {Stem Cell Research \& Therapy},
year = {2026},
month = aug,
doi = {10.1186/s13287-026-05226-8},
url = {https://doi.org/10.1186/s13287-026-05226-8},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Nicotinamide riboside enhances chondrogenic differentiation of human adipose stem cells via inducing SIRT1-mediated deacetylation of SMAD7 and activation of TGF-β/SMAD2/3 pathway
AU - Yichi Xu
AU - Jun Shu
AU - Youbai Chen
AU - Haimiao Wang
AU - Ruoxu Zhang
AU - Muzi Chen
AU - Ran Tao
PY - 2026
DA - 2026/08/08
JO - Stem Cell Research & Therapy
DO - 10.1186/s13287-026-05226-8
UR - https://doi.org/10.1186/s13287-026-05226-8
AB - Mesenchymal stem cells (MSCs) are widely regarded as a promising candidate for cartilage regeneration, and MSC-based therapies have demonstrated therapeutic potential in promoting cartilage repair. Nevertheless, the chondrogenic differentiation efficacy still requires further improvement. This study identified that Nicotinamide Riboside, a precursor of nicotinamide adenine dinucleotide (NAD⁺), significantly enhances chondrogenic differentiation efficiency of human adipose-derived stem cells (hADSCs), primary by activating the TGF-β/SMAD2/3 signaling pathway. Mechanistically, we demonstrated that NR upregulated the expression of SIRT1 and enhanced SIRT1 activity during the induction of chondrogenesis, thereby promoting the deacetylation and subsequent degradation of SMAD7. NR-mediated reduction of SMAD7 results in enhanced phosphorylation of SMAD2/3 and activation of the TGF-β/SMAD2/3 signaling pathway. SIRT1-mediated deacetylation of SMAD7 is a key factor in NR-enhanced chondrogenic differentiation, as disruption of the interaction between SIRT1 and SMAD7 significantly abolishes the promotive effect of NR on chondrogenesis. Collectively, our study demonstrates that NR enhanced chondrogenic differentiation of hADSCs by regulating SIRT1-mediated deacetylation of SMAD7 and activation of TGF-β/SMAD2/3 pathway. NR may therefore possess prospects as a promising supplement for MSC-based cartilage regeneration and repair therapies. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13287-026-05226-8.
SN - 1757-6512
ER -