Genetic and pharmacologic suppression of PPARγ enhances NELL-1-stimulated bone regeneration.

ABSTRACT: Recent investigations into mechanisms behind the development of osteoporosis suggest that suppressing PPARγ-mediated adipogenesis can improve bone formation and bone mineral density. In this study, we investigated a co-treatment strategy to enhance bone formation by combining NELL-1, an osteogenic molecule that has been extensively studied for its potential use as a therapeutic for osteoporosis, with two methods of PPARγ suppression. First, we suppressed PPARγ genetically using lentiviral PPARγ-shRNA in immunocompromised mice for a proof of concept. Second, we used a PPARγ antagonist to suppress PPARγ pharmacologically in immunocompetent senile osteopenic mice for clinical transability. We found that the co-treatment strategy significantly increased bone formation, increased the proliferat

SUBMITTER: Tanjaya J 

PROVIDER: S-EPMC10434299 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature