Arthritogenic alphaviral infection perturbs osteoblast function and triggers pathologic bone loss

• DOI: 10.1073/pnas.1318859111
• Publication Date: 2014-04-15T03:58:43Z
• Authors: Weiqiang Chen; Suan-Sin Foo; Nestor E. Rulli; Adam Taylor; Kuo-Ching Sheng; Lara J. Herrero; Belinda L. Herring; Brett A. Lidbury; Rachel W. Li; Nicole C. Walsh; Natalie A. Sims; Paul N. Smith; Suresh Mahalingam
• Keywords: Adult; Male; 0301 basic medicine; Acid Phosphatase; 610; Osteoclasts; Bone and Bones; Mice; 03 medical and health sciences; Neutralization Tests; 616; Animals; Humans; Growth Plate; Bone Resorption; Osteoblasts; Alphavirus Infections; Interleukin-6; Arthritis; Medical virology; Antibodies, Neutralizing; 3. Good health; Isoenzymes; Mice, Inbred C57BL; Female; Inflammation Mediators

Significance Persistent polyarthritis, which occurs in 30–40% of alphavirus-infected patients, has been proposed to be caused by proinflammatory mediators such as IL-6. In the present study we investigated the susceptibility and response of primary human osteoblasts to Ross River virus (RRV) infection and determined whether infection could result in bone pathology. RRV infection of osteoblasts resulted in increased receptor activator of nuclear factor-kappaB ligand (RANKL) but decreased osteoprotegerin (OPG). We are the first to report that alphavirus infection results in bone loss in an established RRV murine model and that this bone loss is prevented by IL-6 inhibition. These findings reveal that RRV can disrupt bone homeostasis and that osteoblasts play an important role in alphavirus-induced arthritis by regulating IL-6 and contribute to bone loss by disrupting the RANKL/OPG balance.