Moderate-intensity exercise attenuates bone loss in hyperuricemic nephropathic mice

Area of Science:

• Nephrology
• Bone Biology
• Exercise Physiology

Background:

• Hyperuricemia (HUA) is a risk factor for chronic kidney disease (CKD) and hyperuricemic nephropathy (HN), leading to bone loss.
• Exercise is a potential non-pharmacologic intervention for bone health, but its effect on HN-induced bone loss is unclear.

Purpose of the Study:

• To investigate the effects of moderate-intensity exercise on renal injury in HN mice.
• To evaluate the impact of exercise on bone microstructure and the underlying mechanisms in HN mice.

Main Methods:

• A mouse model of hyperuricemic nephropathy was established using potassium oxalate and adenine.
• Mice were divided into control, HUA, exercise control, and exercise HUA groups, with the latter two undergoing 8 weeks of moderate exercise.
• Renal function, bone microarchitecture (micro-CT, HE, TRAP staining), and expression of bone formation/resorption factors (qPCR, Western blotting, immunofluorescence) were analyzed.

Main Results:

• HUA mice exhibited elevated uric acid, impaired renal function, and kidney damage, along with decreased bone quality and altered bone remodeling markers.
• Moderate exercise significantly reduced uric acid levels, improved renal function, and attenuated kidney damage in HUA mice.
• Exercise intervention reversed the negative effects on bone microstructure, increasing bone quality and restoring the balance of bone formation and resorption factors.

Conclusions:

• Hyperuricemic nephropathy causes bone microarchitecture deterioration and bone loss due to imbalanced bone remodeling.
• Moderate-intensity exercise ameliorates renal injury and bone loss in HN mice.
• Exercise effectively regulates osteogenic and osteoclastogenic factors, restoring the balance between bone formation and resorption.