title: Celastrol, an NF-κB inhibitor, ameliorates hypercalciuria and articular cartilage lesions in a mouse model of secondary osteoporosis.
abstract: 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.
authors.affiliation: Department of Orthopedics, YangPu Hospital, TongJi University School of Medicine, Shanghai, 200090, People's Republic of China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, YangPu Hospital, TongJi University School of Medicine, Shanghai, 200090, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Cai
authors.affiliation: Department of Orthopedics, YangPu Hospital, TongJi University School of Medicine, Shanghai, 200090, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, YangPu Hospital, TongJi University School of Medicine, Shanghai, 200090, People's Republic of China.
authors.forename: Anli
authors.initials: A
authors.lastname: Yang
authors.affiliation: Department of Orthopedics, YangPu Hospital, TongJi University School of Medicine, Shanghai, 200090, People's Republic of China. Electronic address: dr_liuliang@163.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D053565:Hypercalciuria / Q000188:drug therapy*; D020738:Leptin / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D058990:Molecular Targeted Therapy; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology*; D010024:Osteoporosis / Q000188:drug therapy* / Q000235:genetics*; D010281:Parathyroid Hormone / Q000097:blood; D053978:Pentacyclic Triterpenes; D014315:Triterpenes / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D020738:Leptin; D016328:NF-kappa B; D010281:Parathyroid Hormone; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; C050414:celastrol
keywords: Cartilage lesions; Celastrol; NF-κB inhibitor; Secondary osteoporosis