Protein kinase D1 conditional null mice show minimal bone loss following ovariectomy

Area of Science:

• Bone Biology
• Endocrinology
• Cell Signaling

Background:

• Conditional ablation of protein kinase D1 (PRKD1) in osteoprogenitor cells reduces bone mass in young male and female mice.
• Estrogen loss, such as through ovariectomy (OVX), typically leads to increased bone resorption and reduced bone mass.

Purpose of the Study:

• To investigate the role of PRKD1 in the bone resorptive response to estrogen loss in adult female mice.

Main Methods:

• Adult female floxed control and PRKD1 conditional knockout (cKO) mice underwent sham surgery or ovariectomy (OVX).
• Bone mineral density (BMD) was measured using DXA.
• Trabecular bone microarchitecture was analyzed using micro-CT.
• Serum levels of pyridinoline crosslinks and RANKL were quantified.

Main Results:

• OVX significantly reduced BMD in control mice but not in cKO mice.
• OVX increased trabecular number and decreased trabecular spacing in cKO mice, but not in controls.
• OVX increased serum pyridinoline crosslinks and RANKL in control mice, but these increases were blunted in cKO mice.

Conclusions:

• PRKD1 plays a critical role in mediating bone loss in response to estrogen deficiency.
• PRKD1 may be a potential therapeutic target for preventing postmenopausal osteoporosis.