Estradiol and RSPO3 regulate vertebral trabecular bone mass independent of each other

Area of Science:

• Bone biology and endocrinology
• Skeletal diseases and aging
• WNT signaling pathways

Background:

• Osteoporosis is a significant age-related skeletal disease with substantial patient suffering and societal costs.
• Declining estrogen levels post-menopause increase bone loss and fracture risk; estrogen therapy can improve bone mass.
• RSPO3, a modulator of WNT signaling, enhances vertebral bone mass and strength in mice and correlates with human fracture risk.

Purpose of the Study:

• To investigate the role of RSPO3 in the bone-sparing effects of estrogen.
• To determine if RSPO3 is necessary for estrogen's protective effects on bone in ovariectomized (OVX) mice.

Main Methods:

• Administered estradiol (E2) to OVX mice and analyzed RSPO3 expression in bone.
• Utilized a mouse model lacking osteoblast-derived RSPO3 (Runx2-creRspo3 mice) to assess E2's effects.
• Evaluated trabecular bone mass, strength in vertebrae, and cortical bone thickness.

Main Results:

• E2 treatment increased RSPO3 expression in OVX mouse bone.
• Osteoblast-specific RSPO3 deficiency reduced vertebral trabecular bone mass and strength.
• E2 enhanced vertebral trabecular bone similarly in RSPO3-deficient and control mice, but required RSPO3 for full cortical bone effects.

Conclusions:

• Osteoblast-derived RSPO3 is crucial for vertebral trabecular bone regulation.
• Estradiol and RSPO3 independently regulate vertebral trabecular bone mass.
• Osteoblast-derived RSPO3 is necessary for the complete estrogenic effect on cortical bone thickness in OVX mice.