title: Fyn promotes proliferation, differentiation, survival and function of osteoclast lineage cells.
abstract: c-Src and Lyn are the only Src family kinases (SFKs) with established activity in osteoclasts (OCs). c-Src promotes function via cytoskeletal organization of the mature resorptive cell while Lyn is a negative regulator of osteoclastogenesis. We establish that Fyn, another SFK, also impacts the OC, but in a manner distinctly different than c-Src and Lyn. Fyn deficiency principally alters cells throughout the osteoclastogenic process, resulting in diminished numbers of resorptive polykaryons. Arrested OC formation in the face of insufficient Fyn reflects reduced proliferation of precursors, in response to M-CSF and retarded RANK ligand (RANKL)-induced differentiation, attended by suppressed activation of the osteoclastogenic signaling molecules, c-Jun, and NF-κB. The anti-apoptotic properties of RANKL are also compromised in cells deleted of Fyn, an event mediated by increased Bim expression and failed activation of Akt. The defective osteoclastogenesis of Fyn-/- OCs dampens bone resorption, in vitro. Finally, while Fyn deficiency does not regulate basal osteoclastogenesis, in vivo, it reduces that stimulated by RANKL by ~2/3. Thus, Fyn is a pro-resorptive SFK, which exerts its effects by prompting proliferation and differentiation while attenuating apoptosis of OC lineage cells.
authors: Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, Missouri 63110, USA. biohjk@knu.ac.kr
authors: Hyun-Ju
authors: HJ
authors: Kim
authors: Julia T
authors: JT
authors: Warren
authors: Shin-Yoon
authors: SY
authors: Kim
authors: Jean C
authors: JC
authors: Chappel
authors: Carl J
authors: CJ
authors: DeSelm
authors: F Patrick
authors: FP
authors: Ross
authors: Wei
authors: W
authors: Zou
authors: Steven L
authors: SL
authors: Teitelbaum
mesh_terms: D000818:Animals; D017209:Apoptosis; D001862:Bone Resorption; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002470:Cell Survival; D051379:Mice; D010010:Osteoclasts / Q000166:cytology*; D051076:Proto-Oncogene Proteins c-fyn / Q000172:deficiency / Q000502:physiology*; D053245:RANK Ligand / Q000502:physiology
chemical_list: D053245:RANK Ligand; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn