Osteocytes regulate primary lymphoid organs and fat metabolism

Area of Science:

• Bone Biology
• Immunology
• Metabolic Health

Background:

• Osteocytes are bone cells that sense mechanical forces.
• Their function in regulating remote organ homeostasis is largely unknown.
• This study investigates the systemic roles of osteocytes.

Purpose of the Study:

• To determine the role of osteocytes in lymphopoiesis and adipose tissue homeostasis.
• To investigate the potential of bone as a central regulator of organ function.

Main Methods:

• Ablation of osteocytes in mice (osteocyte-less [OL] mice).
• Assessment of lymphopenia, white adipose tissue mass, and thymic atrophy.
• Reconstitution of osteocytes and parabiosis experiments with normal mice.
• Hypothalamic ablation in OL mice and subsequent analysis of hepatic steatosis.

Main Results:

• Osteocyte ablation caused severe lymphopenia and loss of white adipose tissue.
• These deficits were reversed upon osteocyte replenishment.
• Hypothalamic ablation in OL mice induced hepatic steatosis, which was rescued by parabiosis.
• Parabiosis with normal mice did not rescue thymic atrophy or fat loss in OL mice.

Conclusions:

• Osteocytes are critical regulators of lymphopoiesis and fat metabolism.
• Bone plays a central role in the homeostasis of multiple organs, including the immune system and adipose tissue.
• Osteocytes communicate systemically to maintain overall metabolic and immune health.