| First Author | Liu Z | Year | 2026 |
| Journal | Life Sci | Volume | 385 |
| Pages | 124121 | PubMed ID | 41317982 |
| Mgi Jnum | J:393489 | Mgi Id | MGI:8460866 |
| Doi | 10.1016/j.lfs.2025.124121 | Citation | Liu Z, et al. (2026) Osteocytic FSH inhibition rescues bone mass and boosts fracture healing in ovariectomized mice. Life Sci 385:124121 |
| abstractText | AIMS: Postmenopausal osteoporosis significantly increases fragility fracture risk. While menopausal estrogen decline coincides with rising follicle-stimulating hormone (FSH), the role of circulating FSH in bone loss remains unclear. This study investigates the direct function of FSH and FSH receptor (FSHR) in bone, focusing on osteocyte-mediated mechanisms. MATERIALS AND METHODS: To probe FSHR function, osteocyte-specific Fshr knockout mice (Dmp1-CreERT; Fshrfl/fl) were generated. Following ovariectomy, Fshr deletion was induced with tamoxifen. We performed RNA-sequencing on femoral cortical bone, validated by digital PCR and ELISA. In vitro assays assessed FSH's effect on PI3K/Akt signaling and osteogenic mineralization. Fracture healing and biomechanics were evaluated using a closed femoral fracture model and three-point bending. KEY FINDINGS: Osteocyte-specific Fshr knockout enhanced bone mineralization, resorption, and formation-resorption coupling, activating the PI3K/Akt pathway. Fshr deletion blocked FSH-mediated PI3K/Akt inhibition and restored osteogenic mineralization in vitro. Knockout mice showed accelerated callus maturation and improved biomechanical healing post-fracture. SIGNIFICANCE: We identify osteocytes as direct FSH target cells. Osteocyte Fshr deletion promotes bone turnover and accelerates fracture repair in ovariectomized mice by enhancing PI3K/Akt signaling. These findings reveal a new pathophysiological mechanism for postmenopausal osteoporosis and suggest a promising therapeutic strategy targeting FSHR. |
