2. Academic Validation
  3. Osteocyte Neuropeptide Y Aggravates Bone Loss in OVX Mice by Inhibiting Preosteoclast Proliferation and PDGF-BB-Induced Type H Vessel Formation Through PI3K/Akt Signaling Pathway

Osteocyte Neuropeptide Y Aggravates Bone Loss in OVX Mice by Inhibiting Preosteoclast Proliferation and PDGF-BB-Induced Type H Vessel Formation Through PI3K/Akt Signaling Pathway

  • Calcif Tissue Int. 2025 Nov 4;116(1):134. doi: 10.1007/s00223-025-01443-0.
Qingchang Chen 1 2 3,  Yan Zhang 4
Affiliations

Affiliations

  • 1 Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 2 Clinical Research Center for Medical Imaging in Hubei Province, Wuhan, China.
  • 3 Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China.
  • 4 Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. [email protected].
PMID: 41186709 DOI: 10.1007/s00223-025-01443-0
Abstract

Type H vessels are sensitive markers of bone mass. Platelet-derived growth factor-BB (PDGF-BB) secreted by preosteoclast was linked with type H vessel generation. Osteocytes (OCY) have been reported to modulate bone metabolism through neuronal induction and active molecules. This study aimed to characterize effect of osteocyte-derived neuropeptide Y (NPY) on ovariectomy (OVX)-induced bone loss in mice and explore the underlying mechanism. Monocytes/macrophages (Mo) were isolated and induced into preosteoclast. Small interfering RNAs were used to knockdown NPY expression in OCY. The culture medium was harvested. Preosteoclast proliferation and PDGF-BB expression were measured by CCK8 analysis and ELISA respectively. Angiogenesis-related experiments were conducted to evaluate the effects of NPY and PDGF-BB on angiogenesis. Western blotting clarified PI3K/Akt pathway involvement in NPY-mediated angiogenesis. In vivo, OVX mice received cultured medium from OCY with NPY knockdown, NPY or vehicle through bone marrow cavity injection. After 2 months, bone samples were collected for µCT and immunofluorescent analysis. Serum OCN, PDGF-BB and VEGF concentrations were assessed by ELISA. It was found that osteocyte-derived NPY inhibits preosteoclast proliferation and PDGF-BB secretion. Culture medium from NPY-stimulated preosteoclasts suppressed migration and tube formation of human microvascular endothelial cells and this effect was reversed following PDGF-BB treatment. NPY negatively regulates preosteoclast PDGF-BB-induced angiogenesis through PI3K/Akt signaling. Importantly, osteocyte NPY exerted detrimental effects on type H vessel formation and aggravated bone loss in OVX mice. Our study identifies a new mechanism by which osteocyte-derived NPY accelerates OVX-induced bone mass loss via inhibiting PDGF-BB secretion and type H vessel formation.

Keywords

Neuropeptide Y; Osteocyte; Osteoporosis; PDGF-BB; Type H vessel.

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