Daidzein alleviates osteoporosis by promoting osteogenesis and angiogenesis coupling

  • PeerJ. 2023 Oct 16:11:e16121. doi: 10.7717/peerj.16121.
Junjie Jia  1  2  3 ,  Ruiyi He  1  2  3 ,  Zilong Yao  1  2 ,  Jianwen Su  1  2 ,  Songyun Deng  1  2 ,  Kun Chen  1  2 ,  Bin Yu  1  2
Affiliations
  • 1. Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
  • 2. Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
  • 3. Department of Orthopaedics, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei, China.
PMID: 37868048 DOI: 10.7717/peerj.16121
Abstract

Background: Postmenopausal osteoporosis and osteoporosis-related fractures are world-wide serious public health problem. Recent studies demonstrated that inhibiting caveolin-1 leads to osteoclastogenesis suppression and protection against OVX-induced osteoporosis. This study aimed to explore the mechanism of caveolin-1 mediating bone loss and the potential therapeutic target.

Methods: Thirty C57BL/6 female mice were allocated randomly into three groups: sham or bilateral ovariectomy (OVX) surgeries were performed for mice and subsequently daidzein or vehicle was administrated to Animals (control, OVX + vehicle and OVX + daidzein). After 8-week administration, femurs were harvested for Micro-CT scan, histological staining including H&E, immunohistochemistry, immunofluorescence, TRAP. Bone marrow endothelial cells (BMECs) were cultured and treated with inhibitors of caveolin-1 (daidzein) or EGFR (erlotinib) and then scratch wound healing and ki67 assays were performed. In addition, cells were harvested for western blot and PCR analysis.

Results: Micro-CT showed inhibiting caveolin-1with daidzein alleviated OVX-induced osteoporosis and osteogenesis suppression. Further investigations revealed H-type vessels in cancellous bone were decreased in OVX-induced mice, which can be alleviated by daidzein. It was subsequently proved that daidzein improved migration and proliferation of BMECs hence improved H-type vessels formation through inhibiting caveolin-1, which suppressed EGFR/Akt/PI3K signaling in BMECs.

Conclusions: This study demonstrated that daidzein alleviates OVX-induced osteoporosis by promoting H-type vessels formation in cancellous bone, which then promotes bone formation. Activating EGFR/Akt/PI3K signaling could be the critical reason.

Keywords
Angiogenesis; Caveolin-1; Daidzein; EGFR; Osteoporosis.
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