transparent gif

 

Ej inloggad.

Göteborgs universitets publikationer

Retinoids stimulate periosteal bone resorption by enhancing the protein RANKL, a response inhibited by monomeric glucocorticoid receptor.

Författare och institution:
H Herschel Conaway (-); Amir Pirhayati (-); Emma Persson (-); Ulrika Pettersson (-); Olle Svensson (-); Catharina Lindholm (Centre for Bone and Arthritis Research & Institutionen för medicin); Petra Henning (Centre for Bone and Arthritis Research & Institutionen för medicin); Jan Tuckermann (-); Ulf H Lerner (Centre for Bone and Arthritis Research & Institutionen för medicin, avdelningen för invärtesmedicin)
Publicerad i:
The Journal of biological chemistry, 286 ( 36 ) s. 31425-36
ISSN:
1083-351X
Publikationstyp:
Artikel, refereegranskad vetenskaplig
Publiceringsår:
2011
Språk:
engelska
Fulltextlänk:
Sammanfattning (abstract):
Increased vitamin A (retinol) intake has been suggested to increase bone fragility. In the present study, we investigated effects of retinoids on bone resorption in cultured neonatal mouse calvarial bones and their interaction with glucocorticoids (GC). All-trans-retinoic acid (ATRA), retinol, retinalaldehyde, and 9-cis-retinoic acid stimulated release of (45)Ca from calvarial bones. The resorptive effect of ATRA was characterized by mRNA expression of genes associated with osteoclast differentiation, enhanced osteoclast number, and bone matrix degradation. In addition, the RANKL/OPG ratio was increased by ATRA, release of (45)Ca stimulated by ATRA was blocked by exogenous OPG, and mRNA expression of genes associated with bone formation was decreased by ATRA. All retinoid acid receptors (RARα/β/γ) were expressed in calvarial bones. Agonists with affinity to all receptor subtypes or specifically to RARα enhanced the release of (45)Ca and mRNA expression of Rankl, whereas agonists with affinity to RARβ/γ or RARγ had no effects. Stimulation of Rankl mRNA by ATRA was competitively inhibited by the RARα antagonist GR110. Exposure of calvarial bones to GC inhibited the stimulatory effects of ATRA on (45)Ca release and Rankl mRNA and protein expression. This inhibitory effect was reversed by the glucocorticoid receptor (GR) antagonist RU 486. Increased Rankl mRNA stimulated by ATRA was also blocked by GC in calvarial bones from mice with a GR mutation that blocks dimerization (GR(dim) mice). The data suggest that ATRA enhances periosteal bone resorption by increasing the RANKL/OPG ratio via RARα receptors, a response that can be inhibited by monomeric GR.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
MEDICIN OCH HÄLSOVETENSKAP ->
Klinisk medicin ->
Endokrinologi och diabetes ->
Endokrinologi
MEDICIN OCH HÄLSOVETENSKAP ->
Klinisk medicin ->
Invärtesmedicin
Nyckelord:
Animals, Animals, Newborn, Bone Resorption, chemically induced, Mice, Osteoprotegerin, Periosteum, pathology, RANK Ligand, agonists, antagonists & inhibitors, Receptors, Glucocorticoid, physiology, Receptors, Retinoic Acid, Retinoids, pharmacology, Tretinoin, pharmacology
Postens nummer:
152128
Posten skapad:
2012-01-10 13:31
Posten ändrad:
2016-08-26 13:47

Visa i Endnote-format

Göteborgs universitet • Tel. 031-786 0000
© Göteborgs universitet 2007