A dual-specific macrophage colony-stimulating factor antagonist of c-FMS and αvβ3 integrin for osteoporosis therapy.

ABSTRACT: There is currently a demand for new highly efficient and specific drugs to treat osteoporosis, a chronic bone disease affecting millions of people worldwide. We have developed a combinatorial strategy for engineering bispecific inhibitors that simultaneously target the unique combination of c-FMS and αvβ3 integrin, which act in concert to facilitate bone resorption by osteoclasts. Using functional fluorescence-activated cell sorting (FACS)-based screening assays of random mutagenesis macrophage colony-stimulating factor (M-CSF) libraries against c-FMS and αvβ3 integrin, we engineered dual-specific M-CSF mutants with high affinity to both receptors. These bispecific mutants act as functional antagonists of c-FMS and αvβ3 integrin activation and hence of osteoclast differentiation in vitro a

SUBMITTER: Zur Y 

PROVIDER: S-EPMC6126843 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature