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001-es BibID:BIBFORM032048
Első szerző:Kertész Zsuzsanna
Cím:Phospholipase C gamma2 is required for basal but not oestrogen deficiency-induced bone resorption / Kertész Zsuzsanna, Győri Dávid, Körmendi Szandra, Fekete Tünde, Kis-Tóth Katalin, Jakus Zoltán, Schett Georg, Rajnavölgyi Éva, Dobó-Nagy Csaba, Mócsai Attila
Dátum:2012
ISSN:0014-2972
Megjegyzések:BACKGROUND: Osteoclasts play a critical role in bone resorption under basal conditions, but they also contribute to pathological bone loss during diseases including postmenopausal osteoporosis. Phospholipase C?2 (PLC?2) is an important signalling molecule in diverse haematopoietic lineages. Here, we tested the role of PLC?2 in basal and ovariectomy-induced bone resorption, as well as in in vitro osteoclast cultures using PLC?2-deficient (PLC?2(-/-) ) mice.MATERIALS AND METHODS: The trabecular architecture of long bone metaphyses was tested by micro-CT and histomorphometric analyses. Postmenopausal osteoporosis was modelled by surgical ovariectomy. Osteoclast development and function, gene expression and PLC?2 phosphorylation were tested on in vitro osteoclast and macrophage cultures.RESULTS: ? PLC?2(-/-) mice had significantly higher trabecular bone mass under basal conditions than wild-type mice. PLC?2 was required for in vitro development and resorptive function of osteoclasts, but not for upregulation of osteoclast-specific gene expression. PLC?2 was phosphorylated in a Src-family-dependent manner upon macrophage adhesion but not upon stimulation by M-CSF or RANKL. Surprisingly, ovariectomy-induced bone resorption in PLC?2(-/-) mice was similar to, or even more robust than, that in wild-type animals. CONCLUSIONS :Our results indicate that PLC?2 participates in bone resorption under basal conditions, likely because of its role in adhesion receptor signalling during osteoclast development. In contrast, PLC?2 does not appear to play a major role in ovariectomy-induced bone loss. These results suggest that basal and oestrogen deficiency-induced bone resorption utilizes different signalling pathways and that PLC?2 may not be a suitable therapeutic target in postmenopausal osteoporosis.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Gene expression
knockout mice
osteoclasts
osteoporosis
phospholipase Cc2
signalling
Megjelenés:European Journal Of Clinical Investigation. - 42 : 1 (2012), p. 49-60. -
További szerzők:Győri Dávid Körmendi Szandra Fekete Tünde (1984-) (immunológus, molekuláris biológus, mikrobiológus) Kis-Tóth Katalin (1975-) (immunológus) Jakus Zoltán Schett, Georg Rajnavölgyi Éva (1950-) (immunológus) Dobó Nagy Csaba (1961-) (fogszakorvos) Mócsai Attila
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