Abstract

Bone health requires adequate bone mass, which is maintained by a critical balance between bone resorption and formation. In our study, we identified beraprost as a pivotal regulator of bone formation and resorption. The administration of beraprost promoted differentiation of mouse bone mesenchymal stem cells (M-BMSCs) through the PI3K–AKT pathway. In co-culture, osteoblasts stimulated with beraprost inhibited osteoclastogenesis in a rankl-dependent manner. Bone mass of p53 knockout mice remained stable, regardless of the administration of beraprost, indicating that p53 plays a vital role in the bone mass regulation by beraprost. Mechanistic in vitro studies showed that p53 binds to the promoter region of neuronal precursor cell-expressed developmentally downregulated 4 (Nedd4) to promote its transcription. As a ubiquitinating enzyme, Nedd4 binds to runt-related transcription factor 2 (Runx2), which results in its ubiquitination and subsequent degradation. These data indicate that the p53–Nedd4–Runx2 axis is an effective regulator of bone formation and highlight the potential of beraprost as a therapeutic drug for postmenopausal osteoporosis.

Highlights

  • Osteoporosis is an age-related bone disease that is associated with an increased risk of fractures[1]

  • Osteoclasts originate from hematopoietic precursor cells and are mainly responsible for absorbing the formed bone, whereas osteoblasts originate from mesenchymal stem cells (MSCs) and are involved in the formation of new bone[5,6]

  • Micro-CT analysis of the distal femur metaphysis suggested that the trabecular bone volume per tissue volume (BV/TV), bone mineral density (BMD), trabecular thickness (Tb.Th), and trabecular number (Tb.N) in OVX groups was significantly decreased compared to that in the sham group, and these indexes returned to higher levels in mice treated with beraprost (Fig. 1A–F)

Read more

Summary

Introduction

Osteoporosis is an age-related bone disease that is associated with an increased risk of fractures[1]. Fractures caused by osteoporosis impose a significant burden on the society and the economy[2]. Postmenopausal osteoporosis accounts for a large proportion of patients with osteoporosis[3]. Osteoporosis is mainly caused by an imbalance in osteoblast-mediated bone formation and osteoclastmediated bone resorption[4]. Osteoclasts originate from hematopoietic precursor cells and are mainly responsible for absorbing the formed bone, whereas osteoblasts originate from mesenchymal stem cells (MSCs) and are involved in the formation of new bone[5,6].

Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call