Targeting of the sonic hedgehog pathway by atractylenolides promotes chondrogenic differentiation of mesenchymal stem cells.
"Molecules that enhance chondrogenic differentiation in mesenchymal stem cells (MSCs) were identified and isolated using an in vitro Gli reporter gene assay in MSCs incorporating a Sonic Hedgehog (Shh) target. Atractylenolide III, which promoted Gli1-mediated transcriptional activity, was isolated from an ethyl acetate extract of the Rhizoma, Atractylodis macrocephalae. After dehydration, atractylenolide III was transformed to atractylenolide I. Both atractylenolides were confirmed by MS, UV, IR, 1H- and 13C-NMR spectra. Atractylenolide III (which contains -OH at the 8-position) and atractylenolide I (which lacks -OH at the 8-position) were found to effectively promote the activity of the Gli promoter. While the hydroxyl group of atractylenolide III was not essential for the effect of atractylenolide, its effect was dependent on Shh signaling. Atractylenolides induced MSCs to differentiate into chondrocytes, as shown by increased expression of specific chondrogenic markers including collagen II, aggrecan and the cartilage related transcription factor, Sox9. Atractylenolides significantly increased the expression of Shh and its target gene Gli-1, indicating that Shh signaling was activated by atractylenolides. Inhibition of Shh signaling reduced the effect of atractylenolides on the chondrogenic phenotype."
"Sonic Hedgehog(Shh), a secreted glycoprotein expressed in the notochord and floor plate, plays a critical role in the control of chondrogenic differentiation."
"Shh promotes chondrogenesis in mesenchymal cells by inducing the expression of Sox9"
"The rhizoma, Atractylodis macrocephalae, was purchased from the Yanghe Pharmacy at Guangzhou University of Chinese Medicine"
"Embryonic day 14 Sprague-Dawley rats"
"Bone marrow was obtained from the femur and tibia of rat."
"MSCs at passage 3 were plated in 24-well plates or 6-well plates at 8000 cells/cm2. Twenty four
hours after cell plating, atractylenolides were added to induce cell differentiation."<-No other growth factors aside from medium!
"Atractylenolides I and III activated the Gli promoter in a dose dependent manner from 3 to 100 μg/mL, while an increase in Gli promoter activity was also observed with Shh"
"Both atractylenolides I and III treatment resulted in a dose-dependent increase in the expression of chondrocyte marker genes, including collagen II and aggrecan [and Sox9]" This increase is dependent on Shh.
"Shh could promote the formation of a larger cartilage template by directly affecting the Sox9 expression level in chondrocytes"
Chemical and ecological evaluation of a genuine Chinese medicine: Atractylodes macrocephala Koidz.
"Atractylenolide I, atractylenolide II and atractylenolide III are all bioactive substances present in Atractylodes macrocephalae"
Unfortunately no homologous compounds were listed. Maybe an expert in TCM like the adult height increase website can help out with profiling this compound because it does seem like it would help with adult increase.
Its been nearly 1.5 years since you have gained 1.5". I m very eager to now yr present status, how much more u hv added.
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