Rictor/mTORC2 loss in osteoblasts impairs bone mass and strength

Area of Science:

• Cellular and Molecular Biology
• Skeletal Biology
• Biochemistry

Background:

• Mammalian target of rapamycin (mTOR) is a key regulator of cell growth, existing in two complexes: mTORC1 and mTORC2.
• mTORC2 comprises distinct components, including rictor, and its role in skeletal anabolism was investigated.

Purpose of the Study:

• To investigate the anabolic role of mTORC2 signaling in the mammalian skeleton.
• To determine the specific function of rictor within osteoblasts in bone maintenance and remodeling.

Main Methods:

• Utilized a Cre/loxp system for targeted deletion of rictor in mature osteoblasts.
• Employed dual energy x-ray absorptiometry (DXA), micro-computed tomography (micro-CT), histomorphometry, and molecular analyses.
• Assessed bone mineral density, lean mass, cortical and trabecular bone architecture, bone turnover, and biomechanical properties.

Main Results:

• Deletion of rictor in osteoblasts (Rictorob(-/-) mice) led to reduced lean mass and bone mineral density.
• Significant impairment of cortical bone mass, thickness, and microarchitecture, with increased porosity.
• Reduced bone turnover due to decreased osteoblast activity and resorption, impacting biomechanical strength.

Conclusions:

• Osteoblast-specific expression of rictor is essential for maintaining normal skeletal remodeling.
• mTORC2 signaling via rictor plays a critical anabolic role, particularly in preserving cortical bone integrity.
• Disruption of rictor in osteoblasts compromises bone mass, architecture, and biomechanical function.