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Resveratrol induces proliferation in preosteoblast cell MC3T3-E1 via GATA-1 activating autophagy
Xiang Liu1, Jun Tao1, Yueyi Yao1
1Science and Technology Achievement Incubation Center, Kunming Medical University, Kunming 650500, China.
Abstract:
Resveratrol (RSV) could promote osteogenic activity, but its clinical application has been hampered in view of its poor bioavailability. Therefore, it is desirable to identify with certainty the molecular target of its bone mass boosting function, which is crucial to the design of an effective therapeutic strategy for the optimal treatment of osteoporosis. Emerging evidence has indicated that GATA-1, an important transcription factor in megakaryocyte and erythrocyte differentiation, can directly activate autophagy in erythrocytes, alluding to its impact on bone metabolism. In light of this, we sought to determine whether GATA-1 would be a putative target by which RSV would act on osteoblast proliferation and, if so, to explore the underlying mechanism involved in the process. We examined the cell viability, colony formation, cell cyclin expression, autophagy level, and the expression levels of GATA-1 and adenosine 5'-monophosphate (AMP)-activated protein kinase α (AMPKα) in osteoblastic cell strain MC3T3-E1. The results showed that RSV promoted the proliferation process in MC3T3-E1 coupled with increased expression of GATA-1 and phosphorylated AMPKα and activated autophagy. When GATA-1 was interfered with siRNA, both autophagy and proliferation were decreased. Administration of the agonist of phosphorylated AMPKα1 (Thr172) promoted the translocation of GATA-1 into the nucleus. Based on the above results, we concluded that RSV induces the proliferation of MC3T3-E1 by increasing GATA-1 expression, which thence activates autophagy; and of note, AMPKα is one of the upstream regulators of GATA-1.
Insights
Resveratrol promotes osteoblast proliferation by increasing GATA-1 expression, which activates autophagy. Adenosine 5'-monophosphate (AMP)-activated protein kinase alpha (AMPKα) acts as an upstream regulator in this process, offering potential osteoporosis treatment strategies.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Biology
Background:
- Resveratrol (RSV) shows potential for promoting osteogenic activity but suffers from poor bioavailability.
- Identifying the molecular targets of RSV's bone-boosting effects is crucial for developing effective osteoporosis therapies.
- GATA-1, a transcription factor involved in blood cell differentiation, has been implicated in bone metabolism via autophagy activation.
Purpose of the Study:
- To investigate if GATA-1 is a molecular target for RSV's osteoblast proliferation effects.
- To elucidate the underlying mechanism by which RSV influences osteoblast proliferation via GATA-1.
- To explore the role of adenosine 5 omino-monophosphate (AMP)-activated protein kinase alpha (AMPKα) in this pathway.
Main Methods:
- Assessed cell viability, colony formation, cell cycle expression, and autophagy levels in MC3T3-E1 osteoblastic cells.
- Quantified the expression of GATA-1 and AMPKα.
- Utilized siRNA to interfere with GATA-1 expression and an agonist to activate AMPKα.
Main Results:
- RSV treatment enhanced MC3T3-E1 cell proliferation, GATA-1 expression, phosphorylated AMPKα levels, and autophagy.
- siRNA-mediated GATA-1 interference reduced both autophagy and proliferation.
- AMPKα activation promoted GATA-1 nuclear translocation.
Conclusions:
- RSV stimulates MC3T3-E1 osteoblast proliferation by upregulating GATA-1, which subsequently activates autophagy.
- AMPKα serves as an upstream regulator of GATA-1 in the context of RSV-induced osteoblast proliferation and autophagy.
- These findings provide insights into a novel therapeutic mechanism for osteoporosis treatment targeting the RSV-GATA-1-AMPKα-autophagy axis.
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