Notwithstanding compelling contribution of NF-κB to the progression of
osteoporosis has been reported, little is known regarding direct inhibition of NF-κB benefiting
osteoporosis. In this study, therefore, we evaluated the role of
celastrol, an NF-κB inhibitor, in a mouse model of secondary
osteoporosis. Animals were divided into three groups as
Sham (control), SO (secondary
osteoporosis) and SO + CA (secondary
osteoporosis treated with
celastrol). Significant decreases in
body weight and body fat were observed following
celastrol treatment in SO group, but
leptin levels were much higher.
Celastrol also exhibited a significant decrease in urinary
calcium excretion. Moreover, other important events were observed after
celastrol treatment, covering substantial decrements in serum concentrations of PTH, TRAP-5b, CTX and DPD, improved structure of articular cartilage and cancellous bone (revealed by H&E and
safranin-O staining), and significant decline in levels of NF-κB (P65), MMP-1, and MMP-9. These findings demonstrated that
celastrol treatment not only improved abnormal lipid metabolism and
hypercalciuria in mice subjected to secondary
osteoporosis, but also ameliorated articular cartilage lesions. Our results provided evidence of targeted
therapy for NF-κB in the clinical treatment of secondary
osteoporosis.