Curcumin attenuates hindlimb unloading-induced bone loss by suppressing NF-κB-mediated osteoclast activation

Area of Science:

• Biomedical Science
• Pharmacology
• Skeletal Biology

Background:

• Microgravity and mechanical unloading cause significant bone loss, posing challenges for space travel and prolonged bed rest.
• Current countermeasures for unloading-induced osteoporosis are insufficient, highlighting the need for effective pharmacological treatments.

Purpose of the Study:

• To investigate the potential of curcumin, a natural polyphenolic compound, as a therapeutic agent against unloading-induced osteoporosis.
• To elucidate the mechanisms by which curcumin affects bone homeostasis under conditions of mechanical unloading.

Main Methods:

• A hindlimb unloading (HU) mouse model was used to simulate microgravity conditions.
• Mice were administered daily doses of curcumin (200 mg/kg).
• Bone mass, microarchitecture, osteoclast function, and relevant molecular signaling pathways (NF-κB) were analyzed.

Main Results:

• Curcumin administration significantly preserved trabecular bone mass and improved microarchitecture (increased BV/TV, Tb.N, Tb.Th; reduced Tb.Sp) in HU mice.
• Curcumin suppressed osteoclast activity and bone resorption, evidenced by reduced TRAP+ cells and downregulation of key osteoclastogenic genes.
• The compound inhibited the NF-κB signaling pathway by reducing p65 and IκBα phosphorylation, thereby restraining osteoclastogenesis.

Conclusions:

• Curcumin demonstrates significant potential in preventing bone loss associated with microgravity or disuse.
• Curcumin's mechanism involves the inhibition of NF-κB signaling, leading to reduced osteoclastogenesis.
• Curcumin represents a promising pharmacological strategy for mitigating unloading-induced osteoporosis with minimal impact on cortical bone.