Abstract : Paget's disease (PDB) is a focal skeletal disorder which affects approximately 2-3 million people over the age 60 years. PDB is characterized by markedly increased osteoclast formation and excess bone resorption . Both viral and genetic factors have been implicated in the pathogenesis of PDB . Mutations (P392L) in the ubiquit in-associated domain of sequestosome 1 (SQSTM1/p62) gene have been widely identified in PDB patients . We previously detected expression of measles virus nucleocapsid (MVNP) transcripts in osteoclasts from patients with PDB and demonstrated that MVNP expression in normal human osteoclasts precursors induce pagetic phenotype in osteoclasts. Also , we showed targeted overexpression of 01 P-1 in the osteoclast lineage inhibits osteoclast formation/bone resorption activity in vivo. Recently, we determined the MVNP and p62P392 L regulated gene expression profiling in preosteoclast cells . In this study, we identified MVNP induced CXCLS expression in preosteoclast cells and that CXCLS induce RANKL, a critical osteoclatogen ic factor expression bone marrow stromal/preosteoblast cells . We demonstrated that OIP-1 inhibit MVNP induced IL-6 expression in bone marrow monocytes. Further, both p62P392 L and MVNP induced IL-23 expression and that OIP-1 inhibits IL-23 expression in preosteoclast cells. These studies provide new insights into the molecular mechanisms underlying the high bone turnover in PDB.