Ovariectomy disregulates osteoblast and osteoclast formation through the T-cell receptor CD40 ligand

• Authors: Jau-Yi Li, Emory University; Hesham Tawfeek, Emory University; Brahmchetna Bedi, Emory University; Xiaoying Yang, Emory University; Jonathan Adams, Emory University; Kristy Y. Gao, Emory University; Majd Zayzafoon, Emory University; M Neale Weitzmann, Emory University; Roberto Pacifici, Emory University
• Journal Title: Proceedings of the National Academy of Sciences
• Volume: Volume 108, Number 2
• Publisher: National Academy of Sciences | 2011-01-11, Pages 768-773
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1073/pnas.1013492108
• Subjects: Health Sciences, Medicine and Surgery
• Keywords: estrogen; osteoporosis

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.