Coupling induction of osteogenesis and type H vessels by pulsed electromagnetic fields in ovariectomy-induced osteoporosis in mice

Qian Wang; Jun Zhou; Xiangxiu Wang; Yang Xu; Zhejun Liang; Xintong Gu; Chengqi He

doi:10.1016/j.bone.2021.116211

Coupling induction of osteogenesis and type H vessels by pulsed electromagnetic fields in ovariectomy-induced osteoporosis in mice

Bone. 2022 Jan:154:116211. doi: 10.1016/j.bone.2021.116211. Epub 2021 Sep 22.

Authors

Qian Wang¹, Jun Zhou², Xiangxiu Wang¹, Yang Xu¹, Zhejun Liang¹, Xintong Gu¹, Chengqi He³

Affiliations

¹ Center of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Rehabilitation Key Laboratory of Sichuan Province, Sichuan University, Chengdu, Sichuan, China.
² Department of Rehabilitation, The First Affiliated Hospital of University of South China, Hengyang, Hunan, China.
³ Center of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Rehabilitation Key Laboratory of Sichuan Province, Sichuan University, Chengdu, Sichuan, China. Electronic address: hxkfhcq@126.com.

PMID: 34560308
DOI: 10.1016/j.bone.2021.116211

Abstract

The growth of blood vessels and osteogenesis are coupled in bone tissue. A specialized subset of CD31^hiEndomucin^hi (CD31^hiEmcn^hi) vascular endothelium in bone has been identified to positively regulate bone formation. Pulsed electromagnetic field (PEMF) can promote the facture healing and reverse the loss of bone mass. However, the underlying mechanisms mediating in the positive effects of PEMF on bone mass accrual remain unclear. In the ovariectomized (OVX) osteoporotic mouse model, PEMF with specific parameters was administrated after 12 weeks of surgery and continued for 8 weeks. μCT analysis, quantitative PCR and Elisa assays were used to assess the PEMF-induced the osteogenesis, while immunostaining and flow cytometry were used to evaluate the abundance of CD31^hiEmcn^hi endothelium in the metaphysis near the growth plate. Administration of PEMF substantially countered OVX-induced bone loss as shown by greater trabecular bone, higher expression of Osterix, PDGFB and Col-1a1 transcripts, and modulation of bone anabolic and catabolic activity. The PEMF-induced osteogenesis was coupled by the expansion of CD31^hiEmcn^hi endothelium as demonstrated by CD31 and Endomucin double-positive immunostaining and flow cytometry. Concurrently, the higher level of HIF-α was found in PEMF-treated mice than in vehicle controls. Notably, inhibition of HIF-1α considerably reduced PEMF-induced osteogenesis, and led to a remarkable decrease of CD31^hiEmcn^hi vessels in the PEMF-treated OVX mice. The present study demonstrated the PEMF-induced coupling promotion of osteogenesis and CD31^hiEmcn^hi endothelial cells in a mouse model of postmenopausal osteoporosis. This coupling effect might be mediated in HIF-1α signaling in CD31^hiEmcn^hi endothelium. These findings open up new directions of al that might enable therapeutic improvement of osteogenesis in patients with osteoporosis.

Keywords: Endothelium; Hypoxia-induced factor-1α; Osteogenesis; Osteoporosis; Pulsed electromagnetic fields.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Electromagnetic Fields
Endothelial Cells / metabolism
Female
Humans
Mice
Osteogenesis*
Osteoporosis* / etiology
Osteoporosis* / metabolism
Ovariectomy