Progranulin Protects Against Osteoporosis by Regulating Osteoclast and Osteoblast Balance via TNFR Pathway

ABSTRACT Osteoporosis is a disease of bone metabolism caused by an imbalance between osteoclast‐mediated bone destruction and osteoblast‐mediated bone formation. Tumour necrosis factor α (TNFα) has been reported to promote osteoclast generation and inhibit osteoblast generation. Progranulin (PGRN), which has a strong anti‐inflammatory effect, interacts with tumour necrosis factor receptor (TNFR). Serum and bone tissues from patients with or without osteoporosis were collected to analyse the relationship between PGRN content and bone metabolic markers. The role of TNFα and PGRN in osteoclast differentiation was explored by using RAW 264.7 cells and BMMs. MC3T3‐E1 cells and BMSCs were used to observe the role of TNFα and PGRN in osteoblast differentiation. The PGRN content in the serum and bone tissues of osteoporosis patients was lower than that in the serum and bone tissues of nonosteoporosis patients. TNFα promoted osteoclast differentiation, while PGRN inhibited this effect by interacting with TNFR1. PGRN inhibited TNFα‐mediated attenuation of osteoblast differentiation by interacting with TNFR1. Moreover, PGRN alone promoted osteoblast differentiation by interacting with TNFR2. Our findings reveal that PGRN can effectively inhibit TNFα‐induced osteoporosis and has a certain osteogenic effect. This discovery might provide a potential target for osteoporosis treatment.