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

Bone. 2021 Sep 22;154:116211. doi: 10.1016/j.bone.2021.116211. Online ahead of print.

Abstract

The growth of blood vessels and osteogenesis are coupled in bone tissue. A specialized subset of CD31hiEndomucinhi (CD31hiEmcnhi) 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 CD31hiEmcnhi 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 CD31hiEmcnhi 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 CD31hiEmcnhi vessels in the PEMF-treated OVX mice. The present study demonstrated the PEMF-induced coupling promotion of osteogenesis and CD31hiEmcnhi endothelial cells in a mouse model of postmenopausal osteoporosis. This coupling effect might be mediated in HIF-1α signaling in CD31hiEmcnhi 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.