P62/sequestosome 1 deficiency accelerates osteoclastogenesis in vitro and leads to Paget's disease-like bone phenotypes in mice.

ABSTRACT: The sequestosome 1 gene encodes the p62 protein and is the major genetic risk factor associated with Paget's disease of bone. In 2004, p62 was reported to up-regulate osteoclast differentiation by activating the transcription factors Nfatc1 and NF-κB. Here, we characterized the osteoclastogenic potential of murine p62^-/--derived cells compared with WT cells. Our data confirmed previous findings indicating that p62 is induced during murine osteoclast differentiation. Surprisingly, an indispensable role for p62 in in vitro osteoclast differentiation was not reproducible because p62-deficient osteoclasts exhibited robust activation of Nfatc1, NF-κB, and osteoclast marker enzymes. Thus, we concluded that in vitro osteoclast differentiation is not negatively influenced

SUBMITTER: Zach F 

PROVIDER: S-EPMC6005453 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature