Lrp1 in osteoblasts controls osteoclast activity and protects against osteoporosis by limiting PDGF-RANKL signaling.

ABSTRACT: Skeletal health relies on architectural integrity and sufficient bone mass, which are maintained through a tightly regulated equilibrium of bone resorption by osteoclasts and bone formation by osteoblasts. Genetic studies have linked the gene coding for low-density lipoprotein receptor-related protein1 (Lrp1) to bone traits but whether these associations are based on a causal molecular relationship is unknown. Here, we show that Lrp1 in osteoblasts is a novel regulator of osteoclast activity and bone mass. Mice lacking Lrp1 specifically in the osteoblast lineage displayed normal osteoblast function but severe osteoporosis due to highly increased osteoclast numbers and bone resorption. Osteoblast Lrp1 limited receptor activator of NF-κB ligand (RANKL) expression in vivo and in vitro through

SUBMITTER: Bartelt A 

PROVIDER: S-EPMC5826921 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature