title: Osteoprotective effects of osthole in a mouse model of 5/6 nephrectomy through inhibiting osteoclast formation.
abstract: The present study aimed to investigate the effects of osthole on osteoclast formation and bone loss in a mouse model of 5/6 nephrectomy. The mice in control and osthole groups were treated 1 month following 5/6 nephrectomy with either a placebo or osthole, respectively. At 2 months post‑nephrectomy, the L4 vertebrae were harvested. The bone mineral density (BMD) of cancellous bone was measured using micro‑CT and tartrate‑resistant acid phosphatase (TRAP) staining was performed to evaluate osteoclast formation. Immunohistochemistry staining and reverse transcription‑quantitative polymerase chain reaction were performed to detect the expression of nuclear factor of activated T‑cells, cytoplasmic‑1 (NFATc‑1), c‑Fos, cathepsin K, Trap, matrix metalloproteinase 9 (Mmp9), osteoprotegerin (Opg) and receptor activator for nuclear factor‑κB ligand (Rankl). Bone marrow cells were cultured with osthole, and osteoclast formation was shown by TRAP staining. Primary calvaria osteoblasts were cultured with osthole, and expression levels of Opg and Rankl were detected. Compared with the sham group, the BMD of mice in model group was significantly reduced. The numbers of osteoclasts and the expression levels of NFATc‑1, c‑Fos, cathepsin K and Mmp9 were significantly increased. Compared with the control group, the mice in the osthole group exhibited increased BMD of the L4 vertebrae, a reduction in osteoclast numbers and decreased expression levels of NFATc‑1, c‑Fos, cathepsin K and Mmp9. In vitro experiments also showed that osteoclast formation was decreased following treatment with osthole. Osteoprotegerin (Opg)/receptor activator for nuclear factor‑κB ligand (Rankl) was upregulated by osthole treatment in the L4 vertebrae and in primary cultures of calvarial osteoblasts. Osthole inhibited osteoclast formation and partially reversed the bone loss induced by 5/6 nephrectomy in mice through the upregulation of OPG/RANKL.
authors: Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, P.R. China.
authors: Xiaofeng
authors: X
authors: Li
authors: Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, P.R. China.
authors: Chunchun
authors: C
authors: Xue
authors: Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, P.R. China.
authors: Libo
authors: L
authors: Wang
authors: Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, P.R. China.
authors: Dezhi
authors: D
authors: Tang
authors: Department of Biochemistry, Rush University Medical Center, Chicago, IL 60607, USA.
authors: Jian
authors: J
authors: Huang
authors: Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, P.R. China.
authors: Yongjian
authors: Y
authors: Zhao
authors: Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, P.R. China.
authors: Yan
authors: Y
authors: Chen
authors: Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, P.R. China.
authors: Dongfeng
authors: D
authors: Zhao
authors: Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, P.R. China.
authors: Qi
authors: Q
authors: Shi
authors: Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, P.R. China.
authors: Yongjun
authors: Y
authors: Wang
authors: Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, P.R. China.
authors: Bing
authors: B
authors: Shu
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D003374:Coumarins / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009392:Nephrectomy; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053244:Osteoprotegerin / Q000235:genetics; D053245:RANK Ligand / Q000235:genetics
chemical_list: D003374:Coumarins; D004365:Drugs, Chinese Herbal; D053244:Osteoprotegerin; D053245:RANK Ligand; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; C046627:osthol