Journal of Cell Communication and Signaling

, Volume 12, Issue 3, pp 561–573 | Cite as

Syringic acid, a phenolic acid, promotes osteoblast differentiation by stimulation of Runx2 expression and targeting of Smad7 by miR-21 in mouse mesenchymal stem cells

  • B. Arumugam
  • K. Balagangadharan
  • N. SelvamuruganEmail author
Research Article


Syringic acid (SA), a phenolic acid, has been used in Chinese and Indian medicine for treating diabetes but its role in osteogenesis has not yet been investigated. In the present study, at the molecular and cellular levels, we evaluated the effects of SA on osteoblast differentiation. At the cellular level, there was increased alkaline phosphatase (ALP) activity and calcium deposition by SA treatment in mouse mesenchymal stem cells (mMSCs). At the molecular level, SA treatment of these cells stimulated expression of Runx2, a bone transcription factor, and of osteoblast differentiation marker genes such as ALP, type I collagen, and osteocalcin. It is known that Smad7 is an antagonist of TGF-β/Smad signaling and is a negative regulator of Runx2. microRNAs (miRNAs) play a key role in the regulation of osteogenesis genes at the post-transcriptional level and studies have reported that Smad7 is one of the target genes of miR-21. We found that there was down regulation of Smad7 and up regulation of miR-21 in SA-treated mMSCs. We further identified that the 3′-untranslated region (UTR) of Smad7 was directly targeted by miR-21 in these cells. Thus, our results suggested that SA promotes osteoblast differentiation via increased expression of Runx2 by miR-21-mediated down regulation of Smad7. Hence, SA may have potential in orthopedic applications.


Bone miR-21 Runx2 Smad7 Syringic acid 



Alkaline phosphatase


Type I Collagen-I


Dulbecco’s modified eagle’s medium


Histone deacetylases


Matrix metalloproteinases


mouse Mesenchymal Stem Cell


3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide




Phosphate-buffered saline


Receptor activator of nuclear factor kappa-B ligand


Reactive oxygen species


Syringic acid


Transforming growth factor- β


Tartrate-resistant acid phosphatase



This work was supported in part by the Department of Biotechnology, India (Grant Nos. BT/PR7792/MED/30/950/2013 and BT/PR15014/BRB/10/1481/2016 to N. S). We thank Dr. N. Subbarayan for advice on statistical analyses.


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Copyright information

© The International CCN Society 2018

Authors and Affiliations

  1. 1.Department of Biotechnology, School of BioengineeringSRM Institute of Science and TechnologyKattankulathurIndia

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