Raloxifene: its ossification-promoting effect on female mesenchymal stem cells.
BACKGROUND
Raloxifene acts like estrogen in preventing bone loss in postmenopausal women, but it selectively activates biological responses in bone tissue. It has a direct effect on osteoblasts' differentiation and bone formation in bone marrow culture. However, the point at which raloxifene has an effect on bone marrow-derived mesenchymal stem cells (MSCs), regardless of sex difference, is not known. The purpose of this study was to examine the osteogenic effect of raloxifene on MSCs derived from female and male rats and to assess the sex difference of raloxifene with or without osteogenic supplements (OSs) in the regulation of bone formation.


METHODS
Female and male rat bone marrow cells were cultured with or without OSs. In each experimental group, 10-6 M or 10-8 M raloxifene was added. As a control, cells were cultured without raloxifene. Histologically, mineralization was assessed by alizarin red S staining. Biochemically, alkaline phosphatase (ALP) activity, calcium content, and osteocalcin content were assessed.


RESULTS
On histological analysis, mineralized nodules were seen on alizarin red S staining in the groups treated with OS. On the biochemical analysis, OS increased ALP activity, calcium content, and osteocalcin content. Among female groups with OSs, 10-6 M raloxifene significantly increased ALP activity, calcium content, and osteocalcin content compared with the controls. Among male groups, raloxifene had negligible effects.


CONCLUSIONS
10-6 M Raloxifene had no ossification-inducing effect on female MSCs, but it had an ossification-promoting effect; it had no osteogenic effect on male MSCs. Therefore, raloxifene has a sex difference with regard to its osteogenic effect on MSCs. Moreover, combined treatment with raloxifene plus OS has an effect on female MSCs. These results provide a useful insight into the possible influence of raloxifene after MSC transplantation in clinical practice.
Department of Orthopaedic Surgery, Nara Medical University, Kashihara, Nara, Japan.
Hiroaki
H
Matsumori
Koji
K
Hattori
Hajime
H
Ohgushi
Yoshiko
Y
Dohi
Yurito
Y
Ueda
Hideki
H
Shigematsu
Nobuhisa
N
Satoh
Hiroshi
H
Yajima
Yoshinori
Y
Takakura
D000818:Animals; D001854:Bone Marrow Cells; D002113:Calcification, Physiologic / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D005260:Female; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D051381:Rats; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D012737:Sex Factors
D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride