title: Phospholipase Cγ2 is required for basal but not oestrogen deficiency-induced bone resorption.
abstract: 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 Cγ2 (PLCγ2) is an important signalling molecule in diverse haematopoietic lineages. Here, we tested the role of PLCγ2 in basal and ovariectomy-induced bone resorption, as well as in in vitro osteoclast cultures using PLCγ2-deficient (PLCγ2(-/-) ) mice.
  
  
  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 PLCγ2 phosphorylation were tested on in vitro osteoclast and macrophage cultures.
  
  
  RESULTS
  PLCγ2(-/-) mice had significantly higher trabecular bone mass under basal conditions than wild-type mice. PLCγ2 was required for in vitro development and resorptive function of osteoclasts, but not for upregulation of osteoclast-specific gene expression. PLCγ2 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 PLCγ2(-/-) mice was similar to, or even more robust than, that in wild-type animals.
  
  
  CONCLUSIONS
  Our results indicate that PLCγ2 participates in bone resorption under basal conditions, likely because of its role in adhesion receptor signalling during osteoclast development. In contrast, PLCγ2 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 PLCγ2 may not be a suitable therapeutic target in postmenopausal osteoporosis.
authors.affiliation: Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Kertész
authors.forename: Dávid
authors.initials: D
authors.lastname: Gyori
authors.forename: Szandra
authors.initials: S
authors.lastname: Körmendi
authors.forename: Tünde
authors.initials: T
authors.lastname: Fekete
authors.forename: Katalin
authors.initials: K
authors.lastname: Kis-Tóth
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Jakus
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
authors.forename: Eva
authors.initials: E
authors.lastname: Rajnavölgyi
authors.forename: Csaba
authors.initials: C
authors.lastname: Dobó-Nagy
authors.forename: Attila
authors.initials: A
authors.lastname: Mócsai
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000201:enzymology*; D002478:Cells, Cultured; D004967:Estrogens / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D010010:Osteoclasts / Q000201:enzymology*; D015663:Osteoporosis, Postmenopausal / Q000201:enzymology*; D010052:Ovariectomy; D051966:Phospholipase C gamma / Q000235:genetics*; D010766:Phosphorylation; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
chemical_list: D004967:Estrogens; D051966:Phospholipase C gamma