Matrix metalloproteinase processing of PTHrP yields a selective regulator of osteogenesis, PTHrP_1-17.

ABSTRACT: Parathyroid hormone-related protein (PTHrP) is a critical regulator of bone resorption and augments osteolysis in skeletal malignancies. Here we report that the mature PTHrP_1-36 hormone is processed by matrix metalloproteinases to yield a stable product, PTHrP_1-17. PTHrP_1-17 retains the ability to signal through PTH1R to induce calcium flux and ERK phosphorylation but not cyclic AMP production or CREB phosphorylation. Notably, PTHrP_1-17 promotes osteoblast migration and mineralization in vitro, and systemic administration of PTHrP_1-17 augments ectopic bone formation in vivo. Further, in contrast to PTHrP_1-36, PTHrP_1-17 does not affect osteoclast formation/function in vitro or in vivo. Finally, immunoprecipitation-

SUBMITTER: Frieling JS 

PROVIDER: S-EPMC7771297 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature