IL6

Interleukin 6 is upregulated 3 fold by LSJL.

Interleukin-6 maintains bone marrow-derived mesenchymal stem cell stemness by an ERK1/2-dependent mechanism.

"interleukin-6 (IL-6) may contribute to the maintenance of MSCs in their undifferentiated state. IL-6 gene expression is significantly higher in undifferentiated MSCs as compared to their chondrogenic, osteogenic, and adipogenic derivatives. MSCs secrete copious amounts of IL-6 protein, which decreases dramatically during osteogenic differentiation. IL-6 is both necessary and sufficient for enhanced MSC proliferation, protects MSCs from apoptosis, inhibits adipogenic and chondrogenic differentiation of MSCs, and increases the rate of in vitro wound healing of MSCs. ERK1/2 activation [is] the key pathway through which IL-6 regulates both MSC proliferation and inhibition of differentiation."

"IL-6 down-regulation in MSCs [occurs] during differentiation and up-regulation [occurs] during de-differentiation or the return to a more stem-like state"

"IL-6 message levels were significantly greater in undifferentiated MSCs compared to osteoblasts, adipocytes, and chondrocytes at days 7 and 14 of differentiation"  LSJL gene expression data took place 49 hours after the first stimulus which is less than 7 days.

"Loss of IL-6 expression decreased MSC proliferation by almost 50% at both 2 and 3 days post-transfection"

"MSC chondrogenic differentiation in the presence of IL-6 exhibited a statistically significant trend toward decreased COL2A1 mRNA transcripts at day 21"

"sGAG levels, as determined by the Blyscan assay, were significantly decreased by IL-6 treatment"

"Stimulation with 10 ng/ml IL-6 for 60 min did not induce activation of STAT3 by phosphorylation"

"After 5 min of stimulation with IL-6, ERK1/2 phosphorylation could be detected. IL-6-mediated ERK1/2 activation peaked 30 min post-IL-6-treatment before returning to baseline levels"

"Following U0126-induced MEK1/2 inhibition, growth analysis revealed that reduced ERK1/2 signaling effectively inhibited IL-6-mediated enhancement of MSC proliferation"

"The IL-6 effect on chondrogenesis was dependent on ERK1/2 activation. The IL-6-mediated decrease in COL2A1 expression was abrogated by co-treatment with U0126"

"A balance between ERK1/2 and STAT3 activation, in terms of signal transduction, has been described in many cell types."