Pristimerin Inhibits Osteoclast Differentiation and Bone Resorption in vitro and Prevents Ovariectomy-Induced Bone Loss in vivo

Abstract

Introduction

Osteoporosis is a metabolic bone disease characterized by reduced bone quantity and microstructure, typically owing to increased osteoclastogenesis and/or enhanced osteoclastic bone resorption, resulting in uncontrolled bone loss, which primarily affects postmenopausal women. In consideration of the severe side effects of current drugs for osteoporosis, new safe and effective medications are necessary. Pristimerin (Pri), a quinone methide triterpene extracted from Celastraceae and Hippocrateaceae members, exhibits potent antineoplastic and anti-inflammatory effects. However, its effect on osteoclasts remains unknown.

Materials and Methods

We evaluated the anti-osteoclastogenic and anti-resorptive effect of Pri on bone marrow-derived osteoclasts and its underlying mechanism in vitro. In addition, the protective effect of Pri on ovariectomy model was also explored in vivo.

Results

In vitro, Pri inhibited osteoclast differentiation and mature osteoclastic bone resorption in a time- and dose-dependent manner. Further, Pri suppressed the expression of osteoclast-related genes and the activation of key proteins. Pri also inhibited the early activation of ERK, JNK MAPK, and AKT signaling pathways in bone marrow-derived macrophages (BMMs), ultimately inhibiting the induction and activation of the crucial osteoclast transcriptional factor nuclear factor of activated T‐cell cytoplasmic 1 (NFATc1). In vivo, consistent with our in vitro data, Pri clearly prevented ovariectomy-induced bone loss.

Conclusion

Our data showed that Pri inhibits the differentiation and activation of osteoclasts in vitro and in vivo, and could be a promising candidate for treating osteoporosis.

Keywords:

• osteoclast
• osteoporosis
• ERK
• JNK
• AKT
• Pri

Acknowledgments

This study was funded by the National Natural Science Foundation of China (grant no. 81572126 and 81871801), the Natural Science Foundation of Zhejiang Province (grant no. LY15H060005), and the Zhejiang Basic Public Welfare Research Project (LGF20H060011 and LGF18H060010).

Abbreviations

Pri, pristimerin; BMMs, bone marrow-derived macrophages; NFATc1, nuclear factor of activated T‐cell cytoplasmic 1; M-CSF, macrophage colony-stimulating factor; RANKL, receptor activation of NF-κB ligand; TRAP, tartrate-resistant acid phosphatase; OVX, ovariectomy.

Disclosure

The paper has been polished by a professional English native speaker.

The authors declare no other potential conflicts of interest for this work.