GPER1 contributes to T3-induced osteogenesis by mediating glycolysis in osteoblast precursors

by Selleckchem | Dec 13 2023

Triiodothyronine (T3) is critical to osteogenesis, which is the key factor in bone growth. Our transcriptomic and metabolomic analysis results indicated that T3 leads to enhanced expression of G protein-coupled estrogen receptor 1 (GPER1) as well as increases in glycolysis metabolite levels. Accordingly, our study aimed to explore the role of GPER1-mediated glycolysis in T3-regulated osteogenesis. The MC3T3-E1 cell line was used as an osteoblast precursor model. After treatment with T3, a GPER1-specific antagonist (G15) and inhibitor of glycolysis (3PO) were used to explore the roles of GPER1 and glycolysis in T3-regulated osteogenesis, as measured by ALP activity, Alizarin red staining intensity and osteogenic molecule expression. Our results showed that T3 promoted osteogenesis-related activity, which was reversed by treatment with G15. In addition, T3 enhanced the glycolytic potential and production of lactic acid (LD) in MC3T3-E1 cells, and treatment with G15 restored the aforementioned effects of T3. Ultimately, the pharmacological inhibition of glycolysis with 3PO blocked the ability of T3 to enhance osteogenic activities. In conclusion, GPER1 mediates glycolysis in osteoblast precursors, which is critical for T3-promoted osteogenesis.

Comments:

It appears that your study has investigated the role of triiodothyronine (T3) in osteogenesis, specifically focusing on its impact on G protein-coupled estrogen receptor 1 (GPER1) and glycolysis in MC3T3-E1 cells, an osteoblast precursor model. Your findings suggest that T3 promotes osteogenesis-related activities in these cells, and this effect is mediated through GPER1 and glycolysis. Here's a summary of your study:

1. **Experimental Setup:**
   - Used MC3T3-E1 cell line as an osteoblast precursor model.
   - T3 treatment was applied to the cells.
   - Used GPER1-specific antagonist (G15) to block GPER1 activity.
   - Used a glycolysis inhibitor (3PO) to block glycolytic activity.

2. **Impact of T3 on Osteogenesis:**
- T3 treatment increased osteogenesis-related activities, such as ALP (alkaline phosphatase) activity, Alizarin red staining intensity, and expression of osteogenic molecules.

3. **Role of GPER1 in T3-Regulated Osteogenesis:**
- T3's promotion of osteogenesis was found to be mediated through GPER1.
- Treatment with G15 (GPER1 antagonist) reversed the osteogenic effects induced by T3.

4. **Impact of T3 on Glycolysis:**
- T3 treatment enhanced glycolytic potential and increased lactic acid production in MC3T3-E1 cells.

5. **Role of Glycolysis in T3-Regulated Osteogenesis:**
- Inhibition of glycolysis with 3PO blocked T3's ability to enhance osteogenic activities.

**Conclusion:**
GPER1, a receptor influenced by T3, plays a crucial role in mediating glycolysis in osteoblast precursors. The glycolytic pathway, in turn, is essential for T3-promoted osteogenesis. This study highlights the intricate molecular mechanisms involved in the process, shedding light on potential therapeutic targets for bone-related disorders.