Celastrol,an NF-κB inhibitor,ameliorates hypercalciuria and articular cartilage lesions in a mouse model of secondary osteoporosis

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. © 2016 japanese pharmacological society.