Novel Dose Dependent Effects of Andrographolide on the Enhancement of
Chondrogenesis and Osteogenesis in Human Mesenchymal Stem Cells
Abstract
Background and Purpose: Andrographolide (AG) is a labdane diterpenoid
herb, which is isolated from the leaves of Andrographis paniculate, and
widely used for its potential medical properties. However, there are no
reports on the effects of AG on the human suprapatellar fat pad of
osteoarthritis patients. In the present study, our goal was to evaluate
the innovative effects of AG on viability and Tri-lineage
differentiation of human mesenchymal stem cells from suprapatellar fat
pad tissues. Experimental approach: The effects of Andrographolide on
viability and differentiation of human primary mesenchymal stem cells
obtained from human suprapatellar fat pad tissues were evaluated by
staining assay. Moreover, the effects on molecular expression were
quantitatively measured by mRNA expression in real time PCR. Key
Results: The results revealed that AG had no cytotoxic effects when the
concentration was less than 12.5 µg/mL. Interestingly, AG had
significantly enhanced, dose dependent, osteogenesis and chondrogenesis
as evidenced by a significantly intensified stain for Alizarin Red S,
Toluidine Blue and Alcian Blue. Moreover, AG can upregulate the
expression of genes related to osteogenic and chondrogenic
differentiation, including Runx2, OPN, Sox9, and Aggrecan in mesenchymal
stem cells from human suprapatellar fat pad tissues. In contrast, AG
suppressed adipogenic differentiation as evidenced by significantly
diminished Oil Red O staining and expression levels for
adipogenic-specific genes for PPAR-γ2 and LPL. Conclusions and
Implications: These findings confirm that AG can specifically enhance
osteogenesis and chondrogenesis of mesenchymal stem cells from human
suprapatellar fat pad tissues. It has potential as a therapeutic agent
derived from natural sources for regenerative medicine.