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Journal of Orthopaedic Surgery and Research

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Open Access 01-12-2023 | Ovariectomy | Research article

ERK-estrogen receptor α signaling plays a role in the process of bone marrow mesenchymal stem cell-derived exosomes protecting against ovariectomy-induced bone loss

Authors: Hui Qi, Enpu Shen, Xiong Shu, Danping Liu, Cheng’ai Wu

Published in: Journal of Orthopaedic Surgery and Research | Issue 1/2023

Abstract

Background

Exosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos) are considered as candidates for osteoporosis (OP) therapy. Estrogen is critical in the maintenance of bone homeostasis. However, the role of estrogen and/or its receptor in BMSC-Exos treatment of OP, as well as its methods of regulation during this process remain unclear.

Methods

BMSCs were cultured and characterized. Ultracentrifugation was performed to collect BMSC-Exos. Transmission electron microscopy, nanoparticle tracking analysis, and western blotting were used to identify BMSC-Exos. We examined the effects of BMSC-Exos on the proliferation, osteogenic differentiation, mineralization, and cell cycle distribution of MG-63 cells. The protein expression of estrogen receptor α (ERα) and the phosphorylation of ERK were investigated through western blotting. We determined the effects of BMSC-Exos on the prevention of bone loss in female rats. The female Sprague–Dawley rats were divided into three groups: the sham group, ovariectomized (OVX) group, and the OVX + BMSC-Exos group. Bilateral ovariectomy was performed in the OVX and OVX + BMSC-Exos groups, while a similar volume of adipose tissue around the ovary was removed in the sham group. The rats in OVX group and OVX + BMSC-Exos group were given PBS or BMSC-Exos after 2 weeks of surgery. Micro-CT scanning and histological staining were used to evaluate the in vivo effects of BMSC-Exos.

Results

BMSC-Exos significantly enhanced the proliferation, alkaline phosphatase activity, and the Alizarin red S staining in MG-63 cells. The results of cell cycle distribution demonstrated that BMSC-Exos increased the proportion of cells in the G2 + S phase and decreased the proportion of cells in the G1 phase. Moreover, PD98059, an inhibitor of ERK, inhibited both the activation of ERK and the expression of ERα, which were promoted by administration of BMSC-Exos. Micro-CT scan showed that in the OVX + BMSC-Exos group, bone mineral density, bone volume/tissue volume fraction, trabecular number were significantly upregulated. Additionally, the microstructure of the trabecular bone was preserved in the OVX + BMSC-Exos group compared to that in the OVX group.

Conclusion

BMSC-Exos showed an osteogenic-promoting effect both in vitro and in vivo, in which ERK-ERα signaling might play an important role.

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Title: ERK-estrogen receptor α signaling plays a role in the process of bone marrow mesenchymal stem cell-derived exosomes protecting against ovariectomy-induced bone loss
Authors: Hui Qi
Enpu Shen
Xiong Shu
Danping Liu
Cheng’ai Wu
Publication date: 01-12-2023
Publisher: BioMed Central
Keywords: Ovariectomy
Osteoporosis
Osteoporosis
Estrogens
Published in: Journal of Orthopaedic Surgery and Research / Issue 1/2023
Electronic ISSN: 1749-799X
DOI: https://doi.org/10.1186/s13018-023-03660-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

ERK-estrogen receptor α signaling plays a role in the process of bone marrow mesenchymal stem cell-derived exosomes protecting against ovariectomy-induced bone loss

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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