# Estrogen promotes the angiogenesis and osteogenesis of bone marrow stromal cells via regulating ESR1/RUNX2 axis

## TL;DR

Estrogen helps prevent osteoporosis by boosting bone and blood vessel growth through the ESR1/RUNX2 pathway in bone marrow cells.

## Contribution

The study reveals a novel mechanism where estrogen regulates bone marrow stromal cell function via the ESR1/RUNX2 axis.

## Key findings

- Estrogen (E2) reduces bone loss and improves bone mass in ovariectomized mice.
- E2 promotes angiogenesis and osteogenesis in bone marrow stromal cells.
- ESR1 interacts with RUNX2 to mediate estrogen's protective effects on bone.

## Abstract

Osteoporosis (OP) is a common bone disease characterized by decreased bone mass and microarchitectural deterioration. This study aimed to investigate the effects of estrogen on OP. Bilateral ovariectomy (OVX) surgery was performed to establish the OP mouse model. Histological analysis was performed using hematoxylin and eosin (HE) staining and alizarin red S (ARS) staining. Angiogenetic factors were determined using enzyme-linked immunosorbent assay (ELISA). Messenger RNA (mRNA) levels were determined using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Protein expression was determined using Western blot. Cellular functions were analyzed using Transwell, tube formation, alkaline phosphatase staining, and ARS staining assay. The co-localization of estrogen receptor alpha (ESR1) and runt-related transcription factor 2 (RUNX2) was determined using the fluorescence in situ hybridization (FISH) assay. The interaction between ESR1 and RUNX2 was determined using the co-immunoprecipitation (Co-IP) assay. We found that 17β-estradiol (E2) alleviated the decrease in bone intensity and mass induced by OVX. E2 promoted the angiogenesis and osteogenesis of bone marrow stromal cells (BMSCs). Mechanistically, E2 predominantly upregulated ESR1. Moreover, mediated nuclear-localization of ESR1 promoted the interaction between ESR1 and RUNX2. Furthermore, ESR1 overexpression promoted the angiogenesis and osteogenesis of BMSCs. Estrogen exerts a protective effect on OP. Estrogen mediates the angiogenesis and osteogenesis of BMSCs by regulating the ESR1/RUNX2 axis.