title: Gab2 plays distinct roles in bone homeostasis at different time points.
abstract: Grb2-associated binder 2 (Gab2) is an adaptor molecule that can be tyrosine phosphorylated by various growth factors and cytokines. Gab2 is known to play a role in signaling pathways downstream of cytokines that regulate bone homeostasis, including M-CSF, RANKL, and IL-6. To clarify the role of Gab2 in bone homeostasis during distinct phases of skeletal development, we compared phenotypic changes in bone homeostasis in Gab2(-/-) mice at two different ages. Although Gab2(-/-) mice showed increased bone volume at both time points, the reasons underlying the increased bone volume differed. At 6 weeks, the increased bone volume was due to enhanced bone resorption and bone formation, indicating that Gab2 plays a negative regulatory role for both osteoclastogenesis and osteoblast differentiation. At 12 weeks, the increased bone volume resulted from reduced osteoclast differentiation, indicating that Gab2 plays a positive regulatory role for osteoclastogenesis. Thus, Gab2 plays opposite roles in osteoclastogenesis during the phases of skeletal development and maintenance.
authors.affiliation: Department of Restorative Dentistry and Endodontology, Osaka University Graduate School of Dentistry, 1-8 Yamada-oka, Suita, Osaka 565-0871, Japan. ito@dent.osaka-u.ac.jp
authors.forename: Shousaku
authors.initials: S
authors.lastname: Itoh
authors.forename: Fumio
authors.initials: F
authors.lastname: Yoshitake
authors.forename: Hiroko
authors.initials: H
authors.lastname: Narita
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Ishihara
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Ebisu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000375:Aging; D000818:Animals; D001846:Bone Development; D006706:Homeostasis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010010:Osteoclasts / Q000166:cytology / Q000502:physiology; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C490894:Gab2 protein, mouse; D010750:Phosphoproteins