onr:"swepub:oai:lup.lub.lu.se:d9744126-ba5c-443a-8937-5504f0f29a3a"
Search: onr:"swepub:oai:lup.lub.lu.se:d9744126-ba5c-443a-8937-5504f0f29a3a" > Differential effect...
- 1 of 1
- Previous record
- Next record
- To hitlist
Differential effects of selective oestrogen receptor modulators (SERMs) tamoxifen, ospemifene and raloxifene on human osteoclasts in vitro
- Michael, H. (author)
-
- Härkönen, Pirkko (author)
- Lund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Department of Translational Medicine,Faculty of Medicine
- Kangas, L. (author)
- show more...
- Vaananen, H. K. (author)
- Hentunen, T. A. (author)
- show less...
- (creator_code:org_t)
- 2009-01-29
- 2007
- English.
- In: British Journal of Pharmacology. - : Wiley. - 1476-5381 .- 0007-1188. ; 151:3, s. 384-395
- Journal article (peer-reviewed)
Abstract
Subject headings
Close
- Background and purpose: Several selective oestrogen receptor modulators ( SERMs) with oestrogen agonist effects in bone cells and without increased risk of breast and endometrial cancer have been developed. Here, we have investigated the effects of different types of SERMs on osteoclast differentiation, bone resorption and apoptosis in vitro. Experimental approach: Human peripheral blood- derived CD14(+) monocytes were cultured on bovine bone slices in the presence of RANKL, M-CSF, TNF-alpha and dexamethasone for seven days. Also, CD14(+) monocytes were co- cultured either with human SaOS-2 or MG-63 osteosarcoma cells, in the presence of parathyroid hormone. Osteoclast cultures were treated with different SERMs. TRACP(+) multinucleated cells and C- terminal telopeptide of type I collagen were used as markers for osteoclast formation and bone resorption, respectively. Key Results: In CD14(+) monocyte cultures, tamoxifen directly inhibited human osteoclast formation and bone resorption, while raloxifene and ospemifene had no inhibitory effect. In the co- cultures either with SaOS- 2 or MG- 63 cells, ospemifene and raloxifene as well as tamoxifen inhibited osteoclast formation in a concentration- dependent manner. The inhibitory effect was associated with an increased production of osteoprotegerin. The anti- oestrogen ICI 182 780 completely reversed the effects of these SERMs. Conclusion and Implications: Tamoxifen had an oestrogen receptor dependent, direct, inhibitory effect o on human osteoclast differentiation and bone resorption, whereas ospemifene and raloxifene required osteoblastic cells to achieve a similar inhibition. The effects of ospemifene and raloxifene were mediated by oestrogen receptors by a mechanism involving paracrine induction of osteoprotegerin in cultures with osteoblast derived osteosarcoma cells.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Keyword
- bone
- osteoclast differentiation
- raloxifene
- tamoxifen
- ospemifene
- osteoprotegerin
- resorption
Publication and Content Type
- art (subject category)
- ref (subject category)
Find in a library
- British Journal of Pharmacology (Search for host publication in LIBRIS)
To the university's database
- 1 of 1
- Previous record
- Next record
- To hitlist
Find more in SwePub
- By the author/editor
- Michael, H.
- Härkönen, Pirkko
- Kangas, L.
- Vaananen, H. K.
- Hentunen, T. A.
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
- MEDICAL AND HEAL ...
- and Basic Medicine
- and Pharmacology and ...
- Articles in the publication
- British Journal ...
- By the university
- Lund University
Search outside SwePub
- Extend your search to:
- Google Book Search
- Google Scholar
Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.
- Copyright © LIBRIS - National Library Systems
- LIBRIS.kb.se
