title: Ovariectomy disregulates osteoblast and osteoclast formation through the T-cell receptor CD40 ligand.
abstract: The bone loss induced by ovariectomy (ovx) has been linked to increased production of osteoclastogenic cytokines by bone marrow cells, including T cells and stromal cells (SCs). It is presently unknown whether regulatory interactions between these lineages contribute to the effects of ovx in bone, however. Here, we show that the T-cell costimulatory molecule CD40 ligand (CD40L) is required for ovx to expand SCs; promote osteoblast proliferation and differentiation; regulate the SC production of the osteoclastogenic factors macrophage colony-stimulating factor, receptor activator of nuclear factor-κB ligand, and osteoprotegerin; and up-regulate osteoclast formation. CD40L is also required for ovx to activate T cells and stimulate their production of TNF. Accordingly, ovx fails to promote bone loss and increase bone resorption in mice depleted of T cells or lacking CD40L. Therefore, cross-talk between T cells and SCs mediated by CD40L plays a pivotal role in the disregulation of osteoblastogenesis and osteoclastogenesis induced by ovx.
authors.affiliation: Division of Endocrinology, Metabolism, and Lipids, Department of Medicine, Emory University, Atlanta, GA 30322, USA.
authors.forename: Jau-Yi
authors.initials: JY
authors.lastname: Li
authors.forename: Hesham
authors.initials: H
authors.lastname: Tawfeek
authors.forename: Brahmchetna
authors.initials: B
authors.lastname: Bedi
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Yang
authors.forename: Jonathan
authors.initials: J
authors.lastname: Adams
authors.forename: Kristy Y
authors.initials: KY
authors.lastname: Gao
authors.forename: Majd
authors.initials: M
authors.lastname: Zayzafoon
authors.forename: M Neale
authors.initials: MN
authors.lastname: Weitzmann
authors.forename: Roberto
authors.initials: R
authors.lastname: Pacifici
mesh_terms: D000818:Animals; D023201:CD40 Ligand / Q000378:metabolism*; D018920:Coculture Techniques; D004967:Estrogens / Q000378:metabolism; D006801:Humans; D008024:Ligands; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology*; D010010:Osteoclasts / Q000166:cytology*; D010024:Osteoporosis / Q000378:metabolism; D053244:Osteoprotegerin / Q000378:metabolism; D010052:Ovariectomy / Q000379:methods; D013601:T-Lymphocytes / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004967:Estrogens; D008024:Ligands; D016328:NF-kappa B; D053244:Osteoprotegerin; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand