Raloxifene inhibits bone loss and improves bone strength through an Opg-independent mechanism.
The osteoblast-derived paracrine factor osteoprotegerin (OPG) is considered to play a key role in inhibition of osteoclast formation and activity. Recently, raloxifene, a nonsteroidal benzothiophene, was found to exert anti-resorptive effects via modulating OPG expression in osteoblasts. To explore whether raloxifene regulates bone metabolism via an OPG-dependant pathway in vivo, we investigated the effects of raloxifene on bone loss in Opg-deficient mice. The results show that bone mineral density and bone strength are increased in mice deficient for Opg after treatment with raloxifene for 30 days. Histomorphometric analysis shows that raloxifene can increase bone trabecular area and decrease the number of osteoclasts in Opg (-/-) mice. Moreover, raloxifene reduces Rankl transcription and serum level of Rankl, which is dramatically increased in Opg knockout mice. These results suggest that raloxifene-induced inhibition of bone resorption may be independent of Opg pathway in mice.
Yan
Mei-zhu
MZ
Department of Geriatrics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200025 Shanghai, China.
Xu
Yong
Y
Gong
Yun-xia
YX
Liu
Jian-min
JM
Lu
Shun-yuan
SY
Huang
Lei
L
Wang
Zhu-gang
ZG
Zhao
Yong-ju
YJ
Pang
Xiao-fen
XF
D000818:Animals; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001862:Bone Resorption / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001842:Bone and Bones / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D002452:Cell Count; D055119:Elastic Modulus; D005260:Female; D005269:Femur / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D008159:Lumbar Vertebrae / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D055595:Mechanical Phenomena; D051379:Mice; D018345:Mice, Knockout; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology; D053244:Osteoprotegerin / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D053245:RANK Ligand / Q000097:blood / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020849:Raloxifene Hydrochloride / Q000494:pharmacology* / Q000627:therapeutic use*; D011897:Random Allocation
D050071:Bone Density Conservation Agents; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D020849:Raloxifene Hydrochloride