Liver X receptors orchestrate osteoblast/osteoclast crosstalk and counteract pathologic bone loss

Kleyer A, Scholtysek C, Bottesch E, Hillienhof U, Beyer C, Distler J, Tuckermann JP, Schett G, Krönke G (2012)


Publication Type: Journal article

Publication year: 2012

Journal

Book Volume: 27

Pages Range: 2442-51

Journal Issue: 12

DOI: 10.1002/jbmr.1702

Abstract

Osteoporosis is characterized by enhanced differentiation of bone-resorbing osteoclasts, resulting in a rapid loss of functional trabecular bone. Bone-forming osteoblasts and osteoblast-derived osteocytes perform a key role in the regulation of osteoclast development by providing both the pro-osteoclastogenic cytokine receptor activator of NF-?B ligand (RANKL) and its natural decoy receptor osteoprotegerin (OPG). By regulating the RANKL/OPG ratio, osteoblasts hence determine the rate of both osteoclast differentiation and bone turnover. Here, we describe a novel role for liver X receptors (LXRs) during the crosstalk of bone-forming osteoblasts and bone-resorbing osteoclasts. By using a system of osteoblast/osteoclast cocultures, we identify LXRs as regulator of RANKL expression and the RANKL/OPG ratio in osteoblasts. Activation of LXRs drastically reduced the RANKL/OPG ratio and interfered with osteoblast-mediated osteoclast differentiation in vitro. During an ovariectomy (OVX)-induced model of postmenopausal osteoporosis, the application of an LXR agonist shifted the RANKL/OPG ratio in vivo, ameliorated the enhanced osteoclast differentiation, and provided complete protection from OVX-induced bone loss. These results reveal an unexpected involvement of LXRs in the regulation of bone turnover and highlight a potential role for LXRs as novel targets in the treatment of osteoporosis and related diseases.

Authors with CRIS profile

Involved external institutions

How to cite

APA:

Kleyer, A., Scholtysek, C., Bottesch, E., Hillienhof, U., Beyer, C., Distler, J.,... Krönke, G. (2012). Liver X receptors orchestrate osteoblast/osteoclast crosstalk and counteract pathologic bone loss. Journal of Bone and Mineral Research, 27(12), 2442-51. https://dx.doi.org/10.1002/jbmr.1702

MLA:

Kleyer, Arnd, et al. "Liver X receptors orchestrate osteoblast/osteoclast crosstalk and counteract pathologic bone loss." Journal of Bone and Mineral Research 27.12 (2012): 2442-51.

BibTeX: Download