Physiological Functions of Osteoblast Lineage and T Cell–Derived RANKL in Bone Homeostasis. (April 2014)

• Record Type: Journal Article
• Authors: Fumoto, Toshio; Takeshita, Sunao; Ito, Masako; Ikeda, Kyoji
• Is Part Of: Journal of bone and mineral research. Volume 29:Number 4(2014:Apr.)
• Page Start: 830
• Page End: 842
• Publication Date: 2014-04
• Subjects: Bones -- Metabolism -- Periodicals; Mineral metabolism -- Periodicals; 612.392
• DOI: 10.1002/jbmr.2096
• Languages: English
• ISSNs: 0884-0431

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>ABSTRACT</title> <sec id="jbmr2096-sec-0001" sec-type="section"> <p>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 <italic>Rankl</italic> specifically in osteoblast lineage cells of mice with the use of an <italic>Osterix‐Cre</italic> 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 <italic>Rankl</italic> 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. © 2014 American Society for Bone and Mineral Research.</p> </sec> </abstract>