[Progranulin aggravates postmenopausal osteoporosis in ovariectomized mice]

Area of Science:

• Biomedical Science
• Osteoporosis Research
• Molecular Biology

Background:

• Osteoporosis is a significant skeletal disorder characterized by low bone mass and microarchitectural deterioration.
• Postmenopausal osteoporosis is often induced in animal models via ovariectomy, mimicking hormonal changes.
• The role of progranulin (PGRN) in bone metabolism, particularly in osteoporosis, remains incompletely understood.

Purpose of the Study:

• To elucidate the specific impact of progranulin (PGRN) on the development of postmenopausal osteoporosis.
• To investigate the molecular mechanisms by which PGRN influences bone density and structure in an ovariectomized mouse model.

Main Methods:

• Ovariectomy was performed on PGRN-knockout (PGRN^-/-) and wild-type mice to establish osteoporosis models.
• Micro-CT scanning and 3D reconstruction were employed for detailed bone microstructural analysis.
• Histological staining (HE, TRAP), immunohistochemistry, qPCR, and Western blot analysis were used to assess cellular and molecular changes, including osteoclast markers and inflammatory factors.

Main Results:

• PGRN^-/- mice exhibited significantly higher bone mineral density (BMD), bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th) compared to wild-type mice.
• Conversely, PGRN^-/- mice showed reduced trabecular separation (Tb.S), indicating improved bone integrity.
• A notable decrease in osteoclast numbers, TRAP mRNA, and the expression of RANKL, TNF-α, MMP9, MMP14, and P65 was observed in PGRN^-/- mice, suggesting reduced bone resorption and inflammation.

Conclusions:

• Progranulin (PGRN) plays a detrimental role, aggravating postmenopausal osteoporosis in ovariectomized mice.
• The absence of PGRN confers a protective effect on bone health by suppressing osteoclastogenesis and inflammatory pathways.
• Targeting PGRN may represent a potential therapeutic strategy for managing postmenopausal osteoporosis.