FSHR targeted Vaccine (Inovio)

To explore the possible mechanisms by which follicle-stimulating hormone (FSH) regulates postmenopausal osteoporosis through the FSH/FSH receptor (FSHr)/G protein/C/EBPβ/heat shock protein 90 alpha (HSP90α) signalling pathways.

We measured serum FSH, luteinising hormone (LH), and HSP90α levels in the serum and adipose tissue of women of childbearing age and menopausal status. In the in vivo studies, 12 B57CL female mice were divided equally into Sham, OVX, and OVX + FSHr Blocker groups. Serum levels of alkaline phosphatase, FSH, and HSP90α, along with StRACP vitality, were determined, and femur micro-computed tomography was performed. Additionally, FSH, FSHr, G protein, C/EBPβ, and HSP90α levels were assessed using quantitative polymerase chain reaction. Finally, we divided the human multiple myeloma cell line U266 into three groups. The activity of tartrate-resistant acid phosphatase (TRAP) in the supernatant at different stages was detected, and myeloma cells were stained with TRAP.

HSP90α levels in adipose tissue supernatant and serum were lower in women of childbearing age than in menopausal women (P < 0.05). Serum FSH and HSP90α levels demonstrated a strong correlation. Treatment with FSHr blockers resulted in decreased FSH, FSHr, G protein, C/EBPβ, and HSP90α levels in mice. TRAP staining of osteoclast-like cells exhibited a significantly higher intensity in the M-CSF + RANKL + recombinant HSP90α group than in the M-CSF + RANKL and blank control groups (P < 0.05).

Our results indicate that FSH promotes HSP90α secretion by adipocytes via the FSHr/G protein/C/EBPβ pathway. This mechanism affects osteoclast activity and exacerbates osteoporosis.