title: Physiological functions of osteoblast lineage and T cell-derived RANKL in bone homeostasis.
abstract: The cytokine RANKL is essential for osteoclast development in bone. The cellular sources of RANKL for support of osteoclast generation under various pathophysiological conditions have remained unclear, however. Here we show that inactivation of Rankl specifically in osteoblast lineage cells of mice with the use of an Osterix-Cre transgene results in typical osteopetrosis in the trabecular compartment of the tibia, with the phenotype being progressively less marked in the femur and vertebrae. In contrast to its effects on trabecular bone, RANKL deficiency in osteoblast lineage resulted in thinning of the femoral cortex in association with suppression of bone formation during the modeling process. Ablation of RANKL specifically in T cells resulted in a moderate but significant increase in tibial trabecular bone. Mice with RANKL deficiency in osteoblast lineage were protected from bone loss induced by ovariectomy as well as from joint destruction associated with arthritis, whereas loss of RANKL in T cells did not confer such protection. Finally, inducible deletion of Rankl selectively in the osteoblasts from 6 to 12 weeks of age resulted in an increase in bone mass in association with reduced bone resorption and formation. Our results thus suggest that RANKL produced by osteoblasts contributes to osteoclast development in vivo.
authors.affiliation: Department of Bone and Joint Disease, National Center for Geriatrics and Gerontology, Aichi, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Fumoto
authors.forename: Sunao
authors.initials: S
authors.lastname: Takeshita
authors.forename: Masako
authors.initials: M
authors.lastname: Ito
authors.forename: Kyoji
authors.initials: K
authors.lastname: Ikeda
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000502:physiology*; D019070:Cell Lineage; D006706:Homeostasis; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000166:cytology*; D053245:RANK Ligand / Q000502:physiology*; D013601:T-Lymphocytes / Q000378:metabolism*; D055114:X-Ray Microtomography
chemical_list: D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse
keywords: OSTEOBLAST; OSTEOCLAST; OSTEOCYTE; RANKL; T CELL